Noon conference case

1. Scleroderma
Ali Philander, Noon conference
11/15/2018

2. Epidemiology
• Incidence 1-2/100,000 and prevalence 19-75/100,000
• Age 30-50 with female predominance (3:1)
• Increased prevalence in populations of European ancestry
• Exposure to Silica dust appears to be a risk factor

3. Types
• Limited- involves skin distal to elbows and knees
• Classic CREST features- Calcinosis cutis, Raynaud, Esophageal dysmotility,
Sclerodactyly, Telangectasia
• More likely to develop PAH and Raynaud’s
• Diffuse- involves chest, abdomen, shoulders
• More likely to develop ILD, fibrosis of other organs

4. Pathophysiology
• Increased amount of normal collagen with accompanying fibroblast
activation which causes fibrosis of skin and other organs
• Etiology unknown, no environmental trigger has been identified
• There are genetic loci associated but these are also shared with other
autoimmune diseases and provide little insight into the generation of
SSc phenotype

5. Diagnosis
• ANA positive 70% of cases
• Anti-Scl-70 (1/3 of cases)
• Anticentromere AB (1/3 of cases)
• RNA polymerase III IgG is diagnostic of systemic sclerosis (1/3 of cases)
• Antibodies are almost always mutually exclusive
• 99.5% specific but only 20-50% sensitive
• Among patients with Raynaud’s and any of these positive antibodies,
there is an increased risk of progression to SSc

6. Manifestations
• Skin- puffy fingers, sclerodactyly, limitation of oral aperture, pruritis,
telangectasias and calcinosis cutis
• MSK- arthralgia, myalgia, tendinosis
• Vascular- Raynaud’s, telangectasias, digital pitting and ulceration
• GI- angiodysplasia of gastric antral mucosa (watermelon stomach), pseudo
obstruction, chronic GERD, esophageal sphincter dysfunction
• Kidney- scleroderma renal crisis- AKI with severe hypertension
• Pulm- ILD with “Velcro like” crackles on exam, PAH with isolated decreased
DLCO
• Cardiac- cardiac fibrosis or cad, conduction disturbances, arrythmia

7. Physical Exam
• Puffy swollen fingers, skin thickening of hands, feet, face, forearms.
Perioral skin tightening with decreased oral aperture
Image from Uptodate

8. More Physical Exam
Mucosal telangectasias
Digital pitting with loss of fingertip
tissue, painful superficial digital
ulcerations
Loss of wrinkles over DIPs, PiPs
Abnormal nailfold capillaroscopy
(microhemorrhages, dilated
capillary loops, capillary drop out)
Image from Uptodate

9. Management- mostly treating complications
• Skin- treat with emollients, treat pruritis
• Vascular- Raynaud’s- calcium channel blockers, topical nitrates,
sildenafil
• GI- GERD- H2 blockers, PPI

10. Management
• MSK- arthralgia, myalgia- sometimes treated with low dose systemic
glucocorticoids, methotrexate
• Pulm- rapidly progressive ILD- cyclophosphamide; PAH with sildenafil
• Renal- Scleroderma Renal Crisis- responds well to ACE
• ACE significantly improves kidney survival and decreases mortality among
patients with SRC
• Mechanism is believed to be mitigation of fibrosis and vascular dysfunction in
the glomerular arterial bed
• Any SSc patient with kidney injury including proteinuria should be placed on
an ACE

11. Monitoring
• Yearly Chest CT to evaluate for ILD
• Yearly PFTs to evaluate for PAH

12. Illness Script- Hypertensive Emergency
Systemic Scleroderma Pheo Hyperaldosteronism
Pathophysiology Fibrosis of the glomerular
arterioles causing
hyperreninemia
Paraganglioma in adrenal gland
that secretes catecholamines
Aldosterone producing adenoma
or bilateral adrenal hyperplasia,
carcinoma, familial
Presentation Encephalopathy, pulmonary
edema, AKI
Encephalopathy, pulmonary
edema, AKI
Palpitations, tremor, anxiety
Encephalopathy, pulmonary
edema, AKI
Concurrent hypokalemia,
metabolic acidosis
Diagnostics CBC, BMR, ANA, Scl-70,
Anticentromere ab, RNA
polymerase III Ab
Plasma free metanephrines, 24
hour urine fractionated
metanephrines and
catecholamines
Elevated plasma aldosterone
concentration, suppressed
plasma renin and PAC/PAC ratio
>20 , Adrenal vein sampling
Therapeutics ACE Alpha blocker followed by beta
blocker
Spironolactone for hyperplasia,
Adrenalectomy for mass

13. Question 1
A 45 year old woman is evaluated for sob and fatigue x6 weeks. She has a 5
year history of diffuse cutaneous systemic sclerosis. Meds are nifedipine,
lisinopril, omeprazole, aspirin. Temp is 99, bp 126/92, pulse 124, rr 26, bmi
25. o2 sat 98% on 2L. Cardiac exam is normal. Velcro like crackles are heard
throughout the chest. Diffuse skin thickening of face, anterior chest, arms
and legs is present. CXR shows ground glass opacities with normal cardiac
silhouette. High resolution CT shows nonspecific interstitial pneumonitis.
Which is the most appropriate treatment?
A) Cyclophosphamide
B) D- penicillamine
C) Infliximab
D) Methotrexate

14. Answer 1
• A- cyclophosphamide for ILD. This is the only treatment shown to
have some benefit in patients with ILD associated with diffuse SSc.
Given for a duration of 1 year. High dose glucocorticoids have unclear
benefit and may precipitate scleroderma renal crisis.

15. Question 2
A 31 year old woman is evaluated in the hospital for headache, blurred
vision, and nausea occurring for the past 12 hours. She has a 2 year history
of diffuse cutaneous systemic sclerosis with recent worsening of Raynaud
phenomenon that is treated with nifedipine. On physical exam, the patient is
alert but somnolent and has altered mental status. BP is 150/92, pulse 104,
95% on ambient air. Exam shows diffuse skin thickening of face, anterior
chest and distal extremities, multiple healed digital pits. Normal cbc, Cr 4.2,
UA with 2+ protein, Urine protein:creatinine ratio 1200. What is the most
appropriate treatment?
A. Captopril
B. Cyclophosphamide
C. Methylpred
D. Sildenafil

16. Answer 2
• A. ACE. SRC occurs in 15% of patients and often causes pulmonary
edema, hypertensive encephalopathy but normal bp present in up to
10%