Graft-versusus-Host Disease bijlagen

Auteur: Ellen Meijer
Autorisator: Sacha Zeerleder

1. Tabel 1: Signs and symptoms of cGVHD
2. Tabel 2: Organ scoring of cGVHD 
3. Acute GvHD response definitions
4. Voedingsschema bij Graft-versus-Hostziekte van het maagdarmkanaal
5. Bereidingsvoorschriften

Symptomatologie en scoren van cGVHD

Tabel 1: Signs and symptoms of cGVHD

Organ or Site	Diagnostic (Sufficient to Establish the Diagnosis of Chronic GVHD)	Distinctive (Seen in Chronic GVHD, but Insufficient Alone to Establish a Diagnosis of Chronic GVHD)	Other Features*	Common (Seen with Both Acute and Chronic GVHD)
Skin	Poikiloderma Lichen planus-like features Sclerotic features Morphea-like features Lichen sclerosus-like features	Depigmentation	Sweat impairment Ichthyosis Keratosis pilaris Hypopigmentation Hyperpigmentation	Erythema Maculopapular rash Pruritus
Nails		Dystrophy Longitudinal ridging, splitting, or brittle features Onycholysis Pterygium unguis Nail loss (usually symmetric; affects most nails)
Scalp and body hair		New onset of scarring or nonscarring scalp alopecia (after recovery from chemoradiotherapy) Scaling, papulosquamous lesions	Thinning scalp hair, typically patchy, coarse, or dull (not explained by endocrine or other causes) Premature gray hair
Mouth	Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis	Xerostomia Mucocele Mucosal atrophy Pseudomembranes Ulcers		Gingivitis Mucositis Erythema Pain
Eyes		New onset dry, gritty, or painful eyes# Cicatricial conjunctivitis Keratoconjunctivitis sicca# Confluent areas of punctate keratopathy	Photophobia Periorbital hyperpigmentation Blepharitis (erythema of the eyelids with edema)
Genitalia	Lichen planus-like features Vaginal scarring or stenosis	Erosions Fissures Ulcers
GI tract	Esophageal web Strictures or stenosis in the upper to mid third of the esophagus		Exocrine pancreatic insufficiency	Anorexia Nausea Vomiting Diarrhea Weight loss Failure to thrive (infants and children)
Liver				Total bilirubin, alkaline phosphatase >2 × ULN,  ALT or AST >2 × ULN
Lung	Bronchiolitis obliterans diagnosed with lung biopsy	Bronchiolitis obliterans diagnosed with PFTs and radiology#		BOOP
Muscles, fascia, joints	Fasciitis Joint stiffness or contractures secondary to sclerosis	Myositis or polymyositis#	Edema Muscle cramps Arthralgia or arthritis
Hematopoietic and immune			Thrombocytopenia Eosinophilia Lymphopenia Hypo- or hypergammaglobulinemia Autoantibodies (AIHA and ITP)
Other			Pericardial or pleural effusions Ascites Peripheral neuropathy Nephrotic syndrome Myasthenia gravis Cardiac conduction abnormality or cardiomyopathy

   
*Can be acknowledged as part of the chronic GVHD symptomatology if the diagnosis is confirmed.
#Diagnosis of chronic GVHD requires biopsy or radiology confirmation (or Schirmer test for eyes).

 

Tabel 2: Organ scoring of cGVHD 

	SCORE 0	SCORE 1	SCORE 2	SCORE 3
PERFORMANCE SCORE: KPS / ECOG / LPS	Asymptomatic and fully active   (ECOG 0; KPS or LPS 100%)	Symptomatic, fully ambulatory, restricted only in physically strenuous activity (ECOG 1, KPS or LPS 80-90%)	Symptomatic, ambulatory, capable of selfcare, >50% of waking hours out of bed (ECOG 2, KPS or LPS 60-70%)	Symptomatic, limited self-care, >50% of waking hours in bed (ECOG 3-4, KPS or LPS <60%)
SKIN Clinical features: Maculopapular rash Lichen planus-like features Papulosquamous lesions or ichthyosis Hyperpigmentation Hypopigmentation Keratosis pilaris Erythema Erythroderma Poikiloderma Sclerotic features Pruritus Hair involvement Nail involvement % BSA involved	No Symptoms	<18% BSA with disease signs but NO sclerotic features	19-50% BSA OR involvement with superficial sclerotic features “not hidebound” (able to pinch)	>50% BSA OR deep sclerotic features “hidebound” (unable to pinch) OR impaired mobility, ulceration or severe pruritus
MOUTH	No symptoms	Mild symptoms with disease signs but not limiting oral intake significantly	Moderate symptoms with disease signs with partial limitation of oral intake	Severe symptoms with disease signs on examination with major imitation of oral intake
EYES Mean tear test (mm): >10 6-10 < 5 Not done	No symptoms	Mild dry eye symptoms not affecting ADL (requiring eyedrops < 3 x per day) OR asymptomatic signs of keratoconjunctivitis sicca	Moderate dry eye symptoms partially affecting ADL (requiring drops > 3 x per day or punctal plugs), WITHOUT vision impairment	Severe dry eye symptoms significantly affecting ADL (special eyeware to relieve pain) OR unable to work because of ocular symptoms OR loss of vision caused by keratoconjunctivitis sicca
GI TRACT	No symptoms	Symptoms such as dysphagia, anorexia, nausea, vomiting, bdominal pain or diarrhea without significant weight loss (<5%)	Symptoms associated with mild to moderate weight loss (5- 15%)	Symptoms associated with significant weight loss >15%, requires nutritional supplement for most calorie needs OR esophageal dilation
LIVER	Normal LFT	Elevated Bilirubin, AP, AST or ALT <2 x ULN	Bilirubin >3 mg/dl (> 50 µmol/L) or Bilirubin, enzymes 2-5 x ULN	Bilirubin or enzymes > 5 x ULN
LUNGS†	No symptoms FEV1 > 80% OR LFS=2	Mild symptoms (shortness of breath after climbing one flight of steps) FEV1 60-79% OR LFS 3-5	Moderate symptoms (shortness of breath after walking on flat ground) FEV1 40-59% OR LFS 6-9	Severe symptoms (shortness of breath at rest; requiring 02)   FEV1 <39% OR LFS 10-12
JOINTS AND FASCIA	No symptoms	Mild tightness of arms or legs, normal or mild decreased range of motion (ROM) AND not affecting ADL	Tightness of arms or legs OR joint contractures, erythema thought due to fasciitis, moderate decrease ROM AND mild to moderate limitation of ADL	Contractures WITH significant decrease of ROM AND significant limitation of ADL (unable to tie shoes, button shirts, dress self etc.)
GENITAL TRACT	No symptoms	Symptomatic with mild signs on exam AND no effect on coitus and minimal discomfort with gynecologic exam	Symptomatic with moderate signs on exam AND with mild dyspareunia or discomfort with gynecologic exam	Symptomatic WITH advanced signs (stricture, labial agglutination or severe ulceration) AND severe pain with coitus or inability to insert vaginal speculum

 Other indicators, clinical manifestations or complications related to chronic GVHD
(check all that apply and assign a score to its severity (0-3) based on its functional impact where applicable (none – 0, mild -1, moderate -2, severe -3)

Esophageal stricture or web___ Ascites (serositis)___ Myasthenia Gravis___ Polymyositis___ Platelets <100,000/μl ___

Pericardial Effusion___ Nephrotic syndrome___ Cardiomyopathy___ Cardiac conduction defects___ Progressive onset___

Pleural Effusion(s)___ Peripheral Neuropathy___ Eosinophilia > 500μl___ Coronary artery involvement___ Other___

 †Pulmonary scoring should be performed using both the symptom and pulmonary function testing (PFT) scale whenever possible. When discrepancy exists between pulmonary symptom or PFT scores the higher value should be used for final scoring. Scoring using the Lung Function Score (LFS) is preferred, but if DLCO is not available, grading using FEV1 should be used. The LFS is a global assessment of lung function after the diagnosis of bronchiolitis obliterans has already been established. The percent predicted FEV1 and DLCO (adjusted for hematocrit but not alveolar volume) should be converted to a numeric score as follows: >80% = 1; 70-79% = 2; 60-69% = 3; 50-59% = 4; 40-49% = 5; <40% = 6. The LFS = FEV1 score + DLCO score, with a possible range of 2-12.
                                                                      

Acute GvHD response definitions

• Complete response:
  The return of acute GvHD to grade O
• Partial response:
  Improvement of at least 1 organ, with no worsening in other organs
• Mixed response:
  Improvement of at least 1 organ, with worsening in at least 1 other organ
• Stable disease:
  No significant change in any organ system
• Progressive disease:
  Progression in at least 1 organ system without improvement in any other organs.

 

Voedingsschema bij Graft-versus-Hostziekte van het maagdarmkanaal

Fase	Klachten	Dieet	Tekenen intolerantie
Darmrust	Darmkrampen Grote hoeveelheid waterige diarree Verlaagd albumine Zeer korte passagetijd Verminderde peristaltiek Misselijkheid en braken	Oraal: NPO PV: volgens energie- en eiwitbehoefte
Introductie orale (vloeibare) voeding	Minimale krampen Diarree < 500ml/24 uur Passagetijd min. 1,5 uur Niet-frequent misselijkheid en braken	Oraal: starten met 60 ml iedere 2-3 uur (enkele dagen) iso-osmotisch, laag-residu, lactosebeperkt PV: volgens energie- en eiwitbehoefte	Toename ontlasting volume of diarree Meer misselijkheid Meer krampen
Introductie vast voedsel	Minimale/geen krampen Gevormde/vaste ontlasting	Oraal: introductie vast voedsel, iedere 3-4 uur: lactosearm, weinig vezels, weinig vet (20-40 g), niet-zuur, geen irriterende* voedingsmiddelen PV: volgens energie- en eiwitbehoefte	Zie boven
Uitbreiding dieet	Minimale/geen krampen Gevormde/vaste ontlasting	Oraal: minimaal lactose, weinig vezels, niet-zuur, geen irriterende voedingsmiddelen, bij vetmalabsorptie: laag vet PV: benodigde aanvulling	Zie boven
Hervatten normaal dieet	Geen krampen Normale ontlasting Normale passagetijd Normaal albumine	Oraal: uitbreiden naar normaal dieet; per dag 1 nieuw product introduceren: zure producten alleen in combinatie met de maaltijd toevoegen, lactose, vezels. Volgorde afhankelijk van eigen voorkeur en tolerantie Indien geen vetdiarree: vetconsumptie voorzichtig uitbreiden PV: stop zodra orale intake toereikend is	Zie boven

 NPO: niets per os, PV: parenterale voeding
*irriterende voedingsmiddelen: zie onderstaand lijstje
Bron: FHCRC/SCCA guidelines long-term follow-up after HSCT http://www.fhcrc.org/science/clinical/ltfu/physician/physician.pdf

 
Irriterende producten:

• Rauwe groenten en fruit
• Gekruide producten
• Vette dingen, zoals worst, gefrituurde producten
• Peulvruchten
• Citrusfruit (-sap)
• Gedroogde vruchten (rozijnen, tutti frutti, enz.)
• Tomatensoep
• Gebonden soepen, gekruide soepen, soep met uit/bonen/bacon/chili/erwten

Introductie orale voeding

1: Vloeibaar
Starten met 1 kopje:

• Thee (niet te sterk)
• Appelsap (aangelengd met water)
• Cranberrysap (aangelengd met water)
• Bouillon

2: Vast:

• Wit brood, beschuit, rijstcrackers, 
• Rijst, pasta, 1 lepel
• Rice crispies / gepofte rijst
• Fruit: ½ banaan, perzik of peer uit blik, geen rauw, vers fruit of andere fruitsoorten uit blik! 
• Gekookte wortelen of sperziebonen
• Tonijn (kleine hoeveelheid)
• Gekookt ei
• Magere ham
• Gestoomde vis
• Kip, kalkoen
• Aardappelen zonder schil

Aandachtspunten bij GVHD van het maagdarmkanaal

• Controleer micronutriënten status (Zn, vitamine A, E, B1, B6, B12, foliumzuur, 25 OH D3); suppleer zonodig vitamines en mineralen
• Overweeg consult diëtist voor vaststellen energie- en voedingsstoffenbehoefte e/o aanvullende diagnostiek
• rustmetabolisme meten via indirecte calorimetrie 
• ontlastingsonderzoek kan meer inzicht in absorptieproblematiek geven; bomcalorimetrie via UMCG: 3 dagen ontlasting sparen en orale intake bijhouden.
• g vet en stikstof in 24 u ontlasting, via klinische chemie VUmc
• evt. nuchter citrulline of citrulline belastingstest 
• evt. Omegaven studie (pilot studie met intraveneuze visolie suppletie bij chronische GVHD-TD)
• Overweeg inschakelen van nurse practitioner met aandachtsgebied GVHD voor het scoren van overige GVHD manifestaties, begeleiding en continuïteit.
• Afhankelijk van de GVH activiteit/klachtenpatroon: parenterale of enterale bijvoeding geven. Zodra de acute fase voorbij is en een soort chronische fase ontstaat blijven veel patiënten ondervoed en voor enige tijd afhankelijk van kunstmatige voeding.

Bereidingsvoorschriften

R/  dexamethason mondspoeling 0,11 mg/ml (voorschrift voor 1000 ml).

1. dexamethasoni natrii phosphas 0.00 H20 Ph.Eur.     143,0  mg
2. natrii metabisulfis 0.00 H20 Ph.Ned.8                       50,0   mg
3. natrii edetas 2.00 H20 Ph.Eur.                                500,0   mg
4. sorbitolum 70 per centum cristallisabile Ph.Eur.         333,0  ml
5. essence frambozen huisnorm                                     1,0     ml
6. solutio methylparabeni conc FNA huisnorm                   6,70    ml
7. aqua ad injectabilia Ph.Eur.                                    ad1000  ml  

Da flacon voor mondspoeling

S/ 6 dd 10 cc, 5 minuten spoelen en uitspugen.
(Maximale bewaartermijn: 6 maanden)

R/  Protopic  0.1% of 0.03%            24 g
 Hypromellose 4000 mpa.s  6 g
S/  mondzalf, tube 30 g, No:…..
Gebruik: 3 dd appliceren, met vinger (wang, tandvlees, tongrand, lippen), nadien ½ uur niet drinken of eten.

Hierbij machtigingsverzoek indienen voor ziektekostenverzekering.

 

Referenties
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Bijbehorende documenten
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Bijlage
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Wijziging t.o.v. vorige versie
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MATCH-GVB-013 versie 1
Geldig juni 2013