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Chronic Graft versus Host Disease Examples May 28, 2012
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Example # 1 Diane is a 36 year old On her clinic note you find the following: Maculopapular rash on her face and upper chest (15% BSA) Food sensitivity, lichen planus-like oral changes on physical exam Dry eyes; using eye drops twice a day
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Example # 1 Does Diane have any diagnostic features of chronic graft versus host disease? Work through possible onset of chronic GVHD worksheet…
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Assessing Skin according to NIH Guidelines Diagnositic: Poikiloderma Lichen planus-like features Sclerotic features Morphea-like feature s Distinctive: Depigmentation Common: Erythema (erythroderma) Pruritis Maculopapular rash Additional features and/or reported symptoms: Ichthyosis Keratosis pilaris Hyperpigmentation Hypopigmentation Papulsquamous lesions Dry skin Limited mobility
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Assessing Skin according to NIH Guidelines Diagnositic: Poikiloderma Lichen planus-like features Sclerotic features Morphea-like feature s Distinctive: Depigmentation Common: Erythema (erythroderma) Pruritis x Maculopapular rash Additional features and/or reported symptoms: Ichthyosis Keratosis pilaris Hyperpigmentation Hypopigmentation Papulsquamous lesions Dry skin Limited mobility
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Assessing Mouth according to NIH Guidelines Diagnostic: Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes Ulcers Common: Gingivitis Mucositis Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums Sensitivity to spicy foods, toothpaste, etc
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Assessing Mouth according to NIH Guidelines Diagnostic: x Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes Ulcers Common: Gingivitis Mucositis Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums x Sensitivity to spicy foods, toothpaste, etc
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Assessing Eyes According to the NIH Guidelines Diagnostic: (None) Distinctive: New onset dry, gritty, or painful eyes Cicatricial conjunctivitis Keratoconjunctivitis sicca Confluent areas of punctuate keratopathy Common: (none) Additional features and/or reported symptoms: Photophobia Periorbital hyperpigmentation Blepharitis Itchy eyes Difficulty opening eyes in the morning Excessive tearing Diminished visual acuity and/or blurring
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Assessing Eyes According to the NIH Guidelines Diagnostic: (None) Distinctive: x New onset dry, gritty, or painful eyes Cicatricial conjunctivitis Keratoconjunctivitis sicca Confluent areas of punctuate keratopathy Common: (none) Additional features and/or reported symptoms: Photophobia Periorbital hyperpigmentation Blepharitis Itchy eyes Difficulty opening eyes in the morning Excessive tearing Diminished visual acuity and/or blurring
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Example # 1 Does Diane have Graft versus Host disease Yes but… Only the lichenoid changes in her mouth are diagnostic of graft versus host disease Once you have determined that the patient has diagnostic features of graft versus host disease then complete cGVHD scoring worksheet
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Scoring Skin cGVHD 0 No Symptoms 1 <18% BSA with disease signs but NO sclerotic features 2 19-50% BSA OR involvement with superficial sclerotic features “not hidebound” (able to pinch) 3 >50% BSA OR deep sclerotic features “hidebound” (unable to pinch) OR impaired mobility, ulceration or severe pruritus Calculating BSA and Rule of 9’s Head / Neck9 % Left upper extremity4.5 % front; 4.5 % back Right upper extremity4.5 % front; 4.5 % back Anterior torso18 % Posterior torso18 % Left lower extremity9 % front; 9 % back Right lower extremity9 % front; 9 % back Genitalia1 %
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Scoring Skin cGVHD 0 No Symptoms X 1 <18% BSA with disease signs but NO sclerotic features 2 19-50% BSA OR involvement with superficial sclerotic features “not hidebound” (able to pinch) 3 >50% BSA OR deep sclerotic features “hidebound” (unable to pinch) OR impaired mobility, ulceration or severe pruritus Calculating BSA and Rule of 9’s Head / Neck9 % Left upper extremity4.5 % front; 4.5 % back Right upper extremity4.5 % front; 4.5 % back Anterior torso18 % Posterior torso18 % Left lower extremity9 % front; 9 % back Right lower extremity9 % front; 9 % back Genitalia1 %
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms 1 Mild symptoms with disease signs but not limiting oral intake significantly 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 >Severe symptoms with disease signs on examination with major limitations of oral intake
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms X 1 Mild symptoms with disease signs but not limiting oral intake significantly 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 >Severe symptoms with disease signs on examination with major limitations of oral intake
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Scoring the Eyes according to NIH Guidelines 0 No Symptoms 1 Mild dry eye symptoms not affecting ADL (requiring drops <3 x per day) OR asymptomatic signs of keratoconjunctivits sicca 2 Moderate dry eye symptoms affecting ADL (requiring drops >3 x per day or punctual plugs), WITHOUT vision impairment 3 Severe dry eye symptoms; significantly affecting ADL (special eye are to relive pain) OR unable to work because of ocular symptoms OR loss of vision caused by keratoconjunctivitis sicca
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Scoring the Eyes according to NIH Guidelines 0 No Symptoms X 1 Mild dry eye symptoms not affecting ADL (requiring drops <3 x per day) OR asymptomatic signs of keratoconjunctivits sicca 2 Moderate dry eye symptoms affecting ADL (requiring drops >3 x per day or punctual plugs), WITHOUT vision impairment 3 Severe dry eye symptoms; significantly affecting ADL (special eye are to relive pain) OR unable to work because of ocular symptoms OR loss of vision caused by keratoconjunctivitis sicca
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Summary of Example # 1 Diane has the following GVHD scoring: Skin score – 1 Mouth score – 1 Eyes score -1
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Global Scoring of Chronic GVHD
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Chronic GVHD Global Score at time of this Assessment for Example # 1 Mild Moderate Severe
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Chronic GVHD Global Score at time of this Assessment for Example # 1 Mild X Moderate Severe
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Example # 2 Julie is a 40 year old female Six month cGVHD assessment – July 27, 2011 On June 10 2011 noted that she started 50mg of prednisone after seeing a respirologist for an FEV1 of 45% and FEV/VC predicted and severe SOB on any exertion Respirologist opinion: bronchiolitis obliterans with interstitial lung disease post stem cell transplant secondary to graft versus host disease She has no other features of cGVHD in any other organ
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Example # 2 Does Julie have any diagnostic or distinctive features of chronic graft versus host disease?
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Assessing Lungs According to NIH Guidelines Diagnostic: Bronchiolitis obliterans diagnosed with lung biopsy Distinctive: Bronchiolitis obliterans diagnosed with PFTs & radiology The following criteria must be present regarding BO: FEV in 1 second/forced vial capacity ratio <0.7 and FEV in 1 second 75% of predicted. Evidence of air trapping or small airway thickening or bronchiectasis on high- resolution chest CT scan (with inspiratory and expiratory cuts) residual volume >120%, or pathologic confirmation of constrictive bronchiolitis. Absence of infection in the respiratory tract, documented with investigations directed by clinical symptoms, such as radiologic studies (radiographs or chest CT scans) or microbiologic cultures (sinus aspiration, URTI screen, sputum culture, or bronchalveolar lavage). Common: Bronchiolitis obliterans organizing pneumonia (BOOP) Additional features and/or reported symptoms: Difficulty breathing Wheezing SOB at rest and/or exertion Dry cough
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Assessing Lungs According to NIH Guidelines Diagnostic: Bronchiolitis obliterans diagnosed with lung biopsy Distinctive: Bronchiolitis obliterans diagnosed with PFTs & radiology The following criteria must be present regarding BO: X FEV in 1 second/forced vial capacity ratio <0.7 and FEV in 1 second 75% of predicted. Evidence of air trapping or small airway thickening or bronchiectasis on high- resolution chest CT scan (with inspiratory and expiratory cuts) residual volume >120%, or pathologic confirmation of constrictive bronchiolitis. Absence of infection in the respiratory tract, documented with investigations directed by clinical symptoms, such as radiologic studies (radiographs or chest CT scans) or microbiologic cultures (sinus aspiration, URTI screen, sputum culture, or bronchalveolar lavage). Common: Bronchiolitis obliterans organizing pneumonia (BOOP) Additional features and/or reported symptoms: Difficulty breathing Wheezing SOB at rest and/or exertion Dry cough
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Example # 2 Issues: CT with inspiratory and expiratory cuts not done Lung biopsy not done No other diagnostic features of chronic graft versus host disease Therefore diagnosis of chronic graft versus host disease can not be made.
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Example # 2 Continues 1 year assessment: Lung: FEV1 – 83%; SOB on walking on flat ground Eyes: dry and gritty; Needs drops about 3-5 times per day she can’t read a book Mouth: Xerostomia; Erythema through the oral mucosa; she feels like mouth has glue in it and has taste disturbance with most foods Liver: AST -92 (> 2 x ULN); ALT 109 (< 2 x ULN)
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Assessing Lungs According to NIH Guidelines Diagnostic: Bronchiolitis obliterans diagnosed with lung biopsy Distinctive: Bronchiolitis obliterans diagnosed with PFTs & radiology The following criteria must be present regarding BO: FEV in 1 second/forced vial capacity ratio <0.7 and FEV in 1 second 75% of predicted. Evidence of air trapping or small airway thickening or bronchiectasis on high- resolution chest CT scan (with inspiratory and expiratory cuts) residual volume >120%, or pathologic confirmation of constrictive bronchiolitis. Absence of infection in the respiratory tract, documented with investigations directed by clinical symptoms, such as radiologic studies (radiographs or chest CT scans) or microbiologic cultures (sinus aspiration, URTI screen, sputum culture, or bronchalveolar lavage). Common: Bronchiolitis obliterans organizing pneumonia (BOOP) Additional features and/or reported symptoms: Difficulty breathing Wheezing SOB at rest and/or exertion Dry cough
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Assessing Lungs According to NIH Guidelines Diagnostic: Bronchiolitis obliterans diagnosed with lung biopsy Distinctive: Bronchiolitis obliterans diagnosed with PFTs & radiology The following criteria must be present regarding BO: FEV in 1 second/forced vial capacity ratio <0.7 and FEV in 1 second 75% of predicted. Evidence of air trapping or small airway thickening or bronchiectasis on high- resolution chest CT scan (with inspiratory and expiratory cuts) residual volume >120%, or pathologic confirmation of constrictive bronchiolitis. Absence of infection in the respiratory tract, documented with investigations directed by clinical symptoms, such as radiologic studies (radiographs or chest CT scans) or microbiologic cultures (sinus aspiration, URTI screen, sputum culture, or bronchalveolar lavage). Common: Bronchiolitis obliterans organizing pneumonia (BOOP) Additional features and/or reported symptoms: Difficulty breathing Wheezing X SOB at rest and/or exertion Dry cough
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Assessing Eyes According to the NIH Guidelines Diagnostic: (None) Distinctive: New onset dry, gritty, or painful eyes Cicatricial conjunctivitis Keratoconjunctivitis sicca Confluent areas of punctuate keratopathy Common: (none) Additional features and/or reported symptoms: Photophobia Periorbital hyperpigmentation Blepharitis Itchy eyes Difficulty opening eyes in the morning Excessive tearing Diminished visual acuity and/or blurring
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Assessing Eyes According to the NIH Guidelines Diagnostic: (None) Distinctive: X New onset dry, gritty, or painful eyes Cicatricial conjunctivitis Keratoconjunctivitis sicca Confluent areas of punctuate keratopathy Common: (none) Additional features and/or reported symptoms: Photophobia Periorbital hyperpigmentation Blepharitis Itchy eyes Difficulty opening eyes in the morning Excessive tearing Diminished visual acuity and/or blurring
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Assessing Mouth according to NIH Guidelines Diagnostic: Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes Ulcers Common: Gingivitis Mucositis Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums Sensitivity to spicy foods, toothpaste, etc
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Assessing Mouth according to NIH Guidelines Diagnostic: Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: X Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes Ulcers Common: Gingivitis Mucositis X Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums X Sensitivity to spicy foods, toothpaste, etc
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Assessing the Liver according to NIH Guidelines Diagnostic: (none) Distinctive: (none) Common: Total bilirubin, alk phos >2x ULN plus ALT or AST>2x ULN
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Assessing the Liver according to NIH Guidelines Diagnostic: (none) Distinctive: (none) Common: X Total bilirubin, alk phos >2x ULN plus ALT or AST>2x ULN
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Example # 2 continues Julie has some distinctive features of cGVHD but no diagnostic features Go back and review with primary physician
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Further review with physician shows… She does have lichen-type features in her mouth… Therefore, a diagnosis of chronic GVHD can be made
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Scoring the Lungs according to NIH Guidelines 0 No symptoms and/or FEV1> 80% OR LFS 3-5 1 Mild symptoms (SOB after climbing one flight of stairs) 2 Moderate symptoms (shortness of breath after walking on flat ground) and/or FEV1 40-59% 3 Severe symptoms (shortness of breath at rest requiring oxygen)
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Scoring the Lungs according to NIH Guidelines 0 No symptoms and/or FEV1> 80% OR LFS 3-5 1 Mild symptoms (SOB after climbing one flight of stairs) X 2 Moderate symptoms (shortness of breath after walking on flat ground) and/or FEV1 40-59% 3 Severe symptoms (shortness of breath at rest; requiring oxygen)
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Scoring the Eyes according to NIH Guidelines 0 No Symptoms 1 Mild dry eye symptoms not affecting ADL (requiring drops < 3 x per day) OR asymptomatic signs of keratoconjunctivits sicca 2 Moderate dry eye symptoms affecting ADL (requiring drops >3 x per day or punctual plugs), WITHOUT vision impairment 3 Severe dry eye symptoms; significantly affecting ADL (special eye are to relive pain) OR unable to work because of ocular symptoms OR loss of vision caused by keratoconjunctivitis sicca
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Scoring the Eyes according to NIH Guidelines 0 No Symptoms 1 Mild dry eye symptoms not affecting ADL (requiring drops < 3 x per day) OR asymptomatic signs of keratoconjunctivits sicca X 2 Moderate dry eye symptoms affecting ADL (requiring drops >3 x per day or punctual plugs), WITHOUT vision impairment 3 Severe dry eye symptoms; significantly affecting ADL (special eye are to relive pain) OR unable to work because of ocular symptoms OR loss of vision caused by keratoconjunctivitis sicca
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms 1 Mild symptoms with disease signs but not limiting oral intake significantly 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 Severe symptoms with disease signs on examination with major limitations of oral intake
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms 1 Mild symptoms with disease signs but not limiting oral intake significantly X 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 Severe symptoms with disease signs on examination with major limitations of oral intake
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Scoring the Liver according to NIH Guidelines 0 Normal LFTs 1 One or more of the following elevated > 2 X ULN: Total Bilirubin, Alk Phos, AST, ALT 2 Total Bilirubin > 3 mg/dl (i.e. > 51 µmol/L) OR One or more of the following elevated 2-5 x ULN: Total Bilirubin, Alk Phos, AST, ALT 3 One or more of the following elevated > 5 x ULN: Total Bilirubin, Alk Phos, AST, ALT
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Scoring the Liver according to NIH Guidelines 0 Normal LFTs X 1 One or more of the following elevated > 2 X ULN: Total Bilirubin, Alk Phos, AST, ALT 2 Total Bilirubin > 3 mg/dl (i.e. > 51 µmol/L) OR One or more of the following elevated 2-5 x ULN: Total Bilirubin, Alk Phos, AST, ALT 3 One or more of the following elevated > 5 x ULN: Total Bilirubin, Alk Phos, AST, ALT
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Summary of Example # 2 Julie has the following GVHD scoring: Lung score – 2 Eye score – 2 Mouth score – 2 Liver Score - 1
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Global Scoring of Chronic GVHD
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Chronic GVHD Global Score at time of this Assessment for Example # 2 Mild Moderate Severe
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Chronic GVHD Global Score at time of this Assessment for Example # 2 Mild Moderate X Severe
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Example # 3 Mark is a 49 year old, 110 days post stem cell transplant On his clinic note you find: He has lichen type changes in his mouth; no taste disturbance Just admitted to hospital in the last 2 days for diarrhea 1.5 litres a day with nausea and vomiting. He has lost 10kg and weighed 85kg at his last visit.
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Assessing Mouth according to NIH Guidelines Diagnostic: Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes Ulcers Common: Gingivitis Mucositis Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums Sensitivity to spicy foods, toothpaste, etc
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Assessing Mouth according to NIH Guidelines Diagnostic: X Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes Ulcers Common: Gingivitis Mucositis Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums Sensitivity to spicy foods, toothpaste, etc
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Assessing the GI Acute and Chronic Chronic Diagnostic: Esophageal web Strictures or stenosis in the upper to mid third of the esophagus Distinctive: (none) Common: Anorexia Nausea Vomiting X Diarrhea X Weight loss Additional features and/or reported symptoms: Exocrine pancreatic insufficiency
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms 1 Mild symptoms with disease signs but not limiting oral intake significantly 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 Severe symptoms with disease signs on examination with major limitations of oral intake
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms X 1 Mild symptoms with disease signs but not limiting oral intake significantly 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 Severe symptoms with disease signs on examination with major limitations of oral intake
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Scoring the GI according to NIH Guidelines 0 No symptoms 1 Symptoms such as dysphagia, anorexia, nausea, vomiting, abdominal pain or diarrhea without significant weight loss (< 5%) 2 Symptoms associated with mild to moderate weight loss (5-15%) 3 Symptoms associated with significant weight loss > 15%, requires nutritional supplement for most calorie needs OR esophageal dilation
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Scoring the GI according to NIH Guidelines 0 No symptoms 1 Symptoms such as dysphagia, anorexia, nausea, vomiting, abdominal pain or diarrhea without significant weight loss (< 5%) X 2 Symptoms associated with mild to moderate weight loss (5-15%) 3 Symptoms associated with significant weight loss > 15%, requires nutritional supplement for most calorie needs OR esophageal dilation
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Example # 3 Organ scores for chronic GVHD for Mark: Mouth - 1 GI - 2
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Global Scoring of Chronic GVHD
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Chronic GVHD Global Score at time of this Assessment for Example # 3 Mild Moderate Severe
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Chronic GVHD Global Score at time of this Assessment for Example # 3 Mild X Moderate Severe
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Example # 4 Doug is a 44 year old with the following findings at his one year assessment Sclerosis involving his arm (18% of skin involved) and not able to extend his arm Oral ulcers, unable to eat spicy foods No other organs involved
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Assessing Skin according to NIH Guidelines Diagnositic: Poikiloderma Lichen planus-like features Sclerotic features Morphea-like feature s Distinctive: Depigmentation Common: Erythema (erythroderma) Pruritis Maculopapular rash Additional features and/or reported symptoms : Ichthyosis Keratosis pilaris Hyperpigmentation Hypopigmentation Papulsquamous lesions Dry skin Limited mobility
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Assessing Skin according to NIH Guidelines Diagnositic: Poikiloderma Lichen planus-like features X Sclerotic features Morphea-like feature s Distinctive: Depigmentation Common: Erythema (erythroderma) Pruritis Maculopapular rash Additional features and/or reported symptoms : Ichthyosis Keratosis pilaris Hyperpigmentation Hypopigmentation Papulsquamous lesions Dry skin X Limited mobility
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Assessing Mouth according to NIH Guidelines Diagnostic: Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes Ulcers Common: Gingivitis Mucositis Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums Sensitivity to spicy foods, toothpaste, etc
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Assessing Mouth according to NIH Guidelines Diagnostic: Lichen-type features Hyperkeratotic plaques Restriction of mouth opening from sclerosis Distinctive: Xerostomia (dry mouth) Mucocele Mucosal atrophy Pseudomembranes X Ulcers Common: Gingivitis Mucositis Erythema Pain Additional features and/or reported symptoms: Chapped lips Bleeding gums X Sensitivity to spicy foods, toothpaste, etc
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Scoring Skin cGVHD 0 No Symptoms 1 <18% BSA with disease signs but NO sclerotic features 2 19-50%BSA OR involvement with superficial sclerotic features “not hidebound” (able to pinch) 3 >50%BSA OR deep sclerotic features “hidebound” (unable to pinch) OR impaired mobility, ulceration or severe pruritus Calculating BSA and Rule of 9’s Head / Neck9 % Left upper extremity4.5 % front; 4.5 % back Right upper extremity4.5 % front; 4.5 % back Anterior torso18 % Posterior torso18 % Left lower extremity9 % front; 9 % back Right lower extremity9 % front; 9 % back Genitalia1 %
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Scoring Skin cGVHD 0 No Symptoms 1 <18% BSA with disease signs but NO sclerotic features 2 19-50%BSA OR involvement with superficial sclerotic features “not hidebound” (able to pinch) X 3 >50%BSA OR deep sclerotic features “hidebound” (unable to pinch) OR impaired mobility, ulceration or severe pruritus Calculating BSA and Rule of 9’s Head / Neck9 % Left upper extremity4.5 % front; 4.5 % back Right upper extremity4.5 % front; 4.5 % back Anterior torso18 % Posterior torso18 % Left lower extremity9 % front; 9 % back Right lower extremity9 % front; 9 % back Genitalia1 %
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms 1 Mild symptoms with disease signs but not limiting oral intake significantly 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 Severe symptoms with disease signs on examination with major limitations of oral intake
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Scoring the Mouth according to NIH Guidelines 0 No Symptoms 1 Mild symptoms with disease signs but not limiting oral intake significantly X 2 Moderate symptoms with disease signs with partial limitation of oral intake 3 Severe symptoms with disease signs on examination with major limitations of oral intake
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Global Scoring of Chronic GVHD
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Chronic GVHD Global Score at time of this Assessment for Example # 4 Mild Moderate Severe
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Chronic GVHD Global Score at time of this Assessment for Example # 4 Mild Moderate X Severe
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Case Study # 5 George is a 52 year old man who is 12 months post HPCT He arrives for his Month 12 study visit Up until his arrival at the clinic there has been no note of a diagnosis of chronic GVHD At the clinic visit the physical exam shows he has significant contractures to his arms and the skin over his shins is immobile (hidebound) George states his arms and shins have been that way for 3 months
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Does George have chronic GVHD? Yes. (contractures and sclerosis/hidebound skin are diagnostic) Should the Part A & B Worksheet be completed retrospectively for Month 9? Yes. The GVHD Scoring Worksheet should also be completed. What is the date of onset (diagnosis)? Month 9. (The patient is a reliable historian.) Should the Part A & B Worksheet be completed at Month 12? It is optional. The Study Visit Worksheet can be completed instead. The GVHD Scoring Worksheet should be completed (It is mandatory). When should the Immunosuppressive Therapy Worksheet be completed re: George’s visits? Month 9 and Month 12.
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Questions?
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