Digital Clubbing of Extremities

1. A Case for Cystic
Fibrosis
Presentation by: Chris Lim

2. History
 CC: “Our daughter always seems to be catching any respiratory illness that
comes around.”
 HPI: 3 year old Caucasian female presents with a severe upper respiratory
infection
 PMHx: Thought to have had a “meconium ileus” at birth
• Issue was said to have resolved itself and there were no
further complications
 Meds: None
 Allergies: None
 Hospitalizations: Unknown
 PSH: Unknown
 SocHx:
• Parents state they do not smoke in home
• Mother states that pt has bad eating habits
• Patient lives at home with parents & is only child
 FmHx:
• Mother stated she has two deceased brothers, both lost to different types of
pneumonia (one brother at age 10, one at age 21)
• Maternal grandmother had a sibling who died from pneumonia (unknown
age)

3. Review of Systems
 General:
+ Cannot gain weight
 Respiratory:
+ Shortness of breath
+ Productive cough
 GI:
+ Greasy, foul-smelling feces

4. Physical Examination
BP: 90/60 Respiratory Rate: 26
Temperature: 100.6°F Pulse: 102 bpm
 Patient appears to be moderately distressed
 Only in 20th percentile for height & weight based on age
 TM’s are intact w/no erythema
 Oropharynx is clear w/no erythema or tonsillar exudate
 Supple neck
 Cardiovascular tachycardia w/no evidence of murmur
 Bilateral expiratory wheezing/rhonci in lungs bilaterally
 Digital clubbing of the extremities

5. Differential Diagnosis
DDx
DD
Ddx
D/Dx


6. The Differential Diagnosis / Differential Diagnostic Procedure
 Systematic method to identify the presence of a disease or
condition, when there are many alternative entities possible
• Based on symptoms, patient history
 Hypothetico- Deductive method, (process of elimination)
• Utilizing medical knowledge
• Flowcharts or algorithms.
• “Working Down the List”
 Potential qualifiers or disease conditions can be viewed as
the hypotheses.
 DDx will guide which tests/panels to order (if necessary).
• “Work-up”
 DDx will influence the flow towards Assessment & Plan.
• Conducted to provide a list to confirm or R/O conditions.
• Re-checking the patient condition and follow-up may
require additional differential diagnosis, to verify the
beneficial or harmful effects of the primary diagnosis.

7. DDx:
I. Symptoms List
II. Possible Causes
III.
a) Most Dangerous/High Stakes
b) Most Likely
c) Low Stakes
d) Unlikely
IV. R/O or treat possible causes

8. Central Problem Statement:
Upper Reparatory Tract Infection, SOB and productive cough
in a 3 y/o Caucasian girl with a history of URI, anorexia,
steatorrhea, tachycardia, bilateral wheezing/rhonchi & digital
clubbing

9. ?

10. POSSIBLE PATHOLOGICAL PROCESSES:
V- Vascular
I – Inflammatory/ Infectious
N - Neoplastic
D – Degenerative/ Deficiency/ Drugs
I – Idiopathic/ Intoxication / Iatrogenic
C – Congenital
A – Autoimmune / Allergic / Anatomic
T - Traumatic
E – Endocrine/ Environmental
M - Metabolic

11. Upper respiratory tract infections
Upper respiratory tract infections occur above the chest and include:
•colds (affecting the nose, throat, and chest)
•Sinusitis (infection of the sinuses)
•throat infection (or pharyngitis — an infection of the throat or pharynx)
•Tonsillitis (infection of the tonsils)
•laryngitis (infection of the larynx or voice box)
•influenza (widespread infection which can affect the nose, throat and,
occasionally, part of the lungs)
•whooping cough (pertussis)
Middle ear infections (otitis media) are a common complication of a
respiratory tract infection.
Where in the respiratory tract infection is the infection?
A respiratory tract infection is an infection anywhere in the respiratory tract (i.e.
the nose, throat and lungs). The infection can be caused by bacteria, a virus or
even fungi.
Lower respiratory tract infections
Lower respiratory tract infections affect the trachea or windpipe and lungs and
include:
•bronchitis (infection of the large airways or bronchi)
•Bronchiolitis (infection of the small airways or bronchioles)
•Croup (infection of the trachea or windpipe in children)
•Influenza (widespread infection of the upper and lower respiratory tract
including the nose, throat and, occasionally, bronchi and lungs)
•Pneumonia (infection of the alveoli and surrounding lung tissue)

12. Respiratory Tract Infection
1) Nasopharynx
2) Larynx
3) Pulmonary
a) Lung Parenchyma
4) Chronic Obstructive Pulmonary
a) Emphysema
b) Chronic Bronchitis
c) Bronchial Asthma

14. Common
Allergies
Asthma or reactive airway disease
Gastroesophageal reflux disease
Infections
• Bronchiolitis
• Bronchitis
• Pneumonia
• Upper respiratory
infection
Obstructive sleep apnea
Uncommon
Bronchopulmonary dysplasia
Foreign body aspiration
Causes of Wheezing in Children and Infants
Rare
Bronchiolitis obliterans
Congenital vascular abnormalities
Congestive heart failure
Cystic fibrosis
Immunodeficiency diseases
Mediastinal masses
Primary ciliary dyskinesia
Tracheobronchial anomalies
Tumor or malignancy
Vocal cord dysfunction

15. Question Indications
How old was the patient when
the wheezing started?
Distinguishes congenital from
noncongenital causes
Did the wheezing start
suddenly?
Foreign body aspiration
Is there a pattern to the
wheezing?
Episodic: asthma
Persistent: congenital or
genetic cause
Is the wheezing associated
with a cough?
GERD, sleep apnea, asthma,
allergies
Is the wheezing associated
with feeding?
GERD
Is the wheezing associated
with multiple respiratory
illnesses?
Cystic fibrosis,
immunodeficiency
Is the wheezing associated
with a specific season?
Allergies: fall and spring
Croup: fall to winter
Human bocavirus*
Human metapneumovirus:
December through April
RSV: fall to spring
Does the wheezing get better
or worse when the patient
changes position?
Tracheomalacia, anomalies of
the great vessels
Is there a family history of
wheezing?
Infections, allergic triad
Questions to Distinguish the Etiology of Wheezing in Children
GERD = gastroesophageal
reflux disease
RSV = respiratory syncytial
virus.

16. Signs and symptoms Presumptive diagnosis Further evaluation
Associated with feeding, cough, and
vomiting
Gastroesophageal reflux disease 24-hour pH monitoring Barium
swallow
Associated with positional changes Tracheomalacia; anomalies of the great
vessels
Angiography
Bronchoscopy
CT Chest radiographyor MRI
Echocardiography
Auscultatory crackles, fever Pneumonia Chest radiography
Episodic pattern, cough; patient
responds to bronchodilators
Asthma Allergy testing
Pulmonary function testing
Trial of albuterol (Proventil)
Exacerbated by neck flexion; relieved
by neck hyperextension
Vascular ring Angiography
Barium swallow
Bronchoscopy
Chest radiography
CT or MRI
Heart murmurs or cardiomegaly,
cyanosis without respiratory distress
Cardiac disease Angiography
Chest radiography
Echocardiography
History of multiple respiratory illnesses;
failure to thrive
Cystic fibrosis or immunodeficiency Ciliary function testing
Immunoglobulin levels
Sweat chloride testing
Seasonal pattern, nasal flaring,
intercostal retractions
Bronchiolitis (RSV), croup, allergies Chest radiography
Stridor with drooling Epiglottitis Neck radiography
Sudden onset of wheezing and
choking
Foreign body aspiration Bronchoscopy
Differential Diagnosis of Wheezing According to Characteristic Signs and Symptoms

17. Pediatric
Aspergillosis is a
severe
complication of
Cystic Fibrosis

20. Bronchiectasis can
cause Cystic Fibrosis

21. ?

22. DDx Summary:
I. Symptoms List
• CC & HPI
II. Possible Causes
• (Slides 9-12)
III.
a) Most Dangerous/High Stakes
• Bronchiectasis*
b) Most Possible
• Cystic fibrosis
c) Low Stakes
• Pediatric aspergillosis
d) Unlikely
• Pediatric gastroesophageal reflux
• Pediatric hypersensitivity pneumonitis
IV. R/O or treat possible causes
• Workup of DDx→Dx
*Bronchiectasis—permanent dilation of the
bronchioles, loss of airway, air is trapped, may
be concomitant with tumor or necrotizing
infection.

23. Working Diagnosis:
Cystic fibrosis

24. Cystic fibrosis:
clinical presentation
 Cystic fibrosis is caused by a mutation in an ion channel, this
affects exocrine secretions in multiple organ systems.
• Respiratory manifestations include persistent, productive cough;
hyperinflation of the lung fields on chest radiographs; and
pulmonary function tests consistent with obstructive airway
disease. Sinus disease is present in a majority of patients.
• Pancreatitis and insufficient exocrine function of the pancreas
(leading to CF-related diabetes) are common symptoms, along
with oily stools and malabsorption of fats and proteins,.
• Reduced bone mineral content and hypertrophic
osteoarthropathy (abnormal proliferation of skin and osseous
tissue at the distal parts of the extremities, leading to digital
clubbing) may also be observed in patients with CF.
• Neonates frequently present with meconium ileus and
demonstrate poor weight gain.

25. Cystic fibrosis:
diagnostic criteria
 A diagnosis of cystic fibrosis requires clinical symptoms
consistent with CF in at least one organ system as well as
evidence of a dysfunctional CFTR (cystic fibrosis
transmembrane conductance receptor).
• Evidence of a dysfunctional CFTR can come in the form of
elevated sweat chloride (≥60 mmol/L in a sufficient quantity
[75 mg/15μL in 30 minutes] of collected sweat), abnormal
nasal potential differences (NPD), or presence of two
disease-causing mutations in CFTR in each parent allele.
 The patient presented with a severe upper respiratory
infection as well as a history of recurring respiratory
illness. She has frequent greasy stools and a history
remarkable for meconium ileus—an obstruction of the
distal small intestine in neonates.
 Physical exam finding reveal that she is only in the 20th
percentile for height and weight. Her extremities
revealed digital clubbing.

27. Epidemiology
 Most common life-limiting autosomal recessive disease in
Caucasions.
 Point mutation in the Cystic Fibrosis Transmembrane
Conductance Regulator (CFTR) protein also known as an
ATP-binding cassette (ABC) transporter.
 Most common mutation is ΔF508-CFTR, occurs in >90% U.S.
patients and 66% of all CF worldwide.
 CFTR gene is located on chromosome 7q31.2
 230,000 base pairs and is 1,480 amino acids long
 CFTR protein contains two ATP-hydrolyzing domains
composed of 6 α-helices each.

28. Requires the presence of two copies to
manifest symptoms of disease.

29. Epidemiology cont.
 Chloride ion channels are used in creating digestive
juices, mucus, and sweat.
 Around 1,500 other known mutations.
- Point mutation causes misfold in the protein.
- Protein remains trapped in the ER.
- Disrupts chloride transport.
 Mutated CFTR proteins don’t allow chloride, iodine, or
thiocyanate to cross the cell membrane.

30. Pathophysiology
Lungs
 Normal lung epithelium secretes chloride into the airway
lumen via CFTR.
 Impaired chloride transport leads to:
• Increased sodium and water absorption from airways
into the blood.
• Dehydration of mucociliary blanket coating epithelial
cells.
• Accumulation of thick mucus in the airways
• Nutrient rich environment for reoccurring pulmonary
infections.
• Burkholderia cepacia, Haemophilus influenza,
Pseudomonas aeruginosa, and Staphyloccus aureus.
• Excessive neutrophilic inflammation

31. Pathophysiology cont.
Gastrointestinal
 80-90% of CF individuals have abnormal pancreatic
function.
 Gastrointestinal problems with cystic fibrosis due to inability
of the pancreas to supply digestive enzymes to the
intestine.
 Volume of pancreatic enzymes decreases—pancreas
secretes thick mucus
• Causes malabsorption of proteins and influences
absorption of vitamin A, D, E, K
 Abdominal pain, diarrhea, and steatorrhea is common.
 20% of individuals with CF present with meconium ileus.
 Meconium ileus is not related to the severity of CF.

33. Diagnostic Tests:
Sweat Chloride
Chloride
Concentration for
Children and Adults
Result
≤ 39 mmol/L Normal
40 - 59 mmol/L Intermediate
≥ 60 mmol/L Indicative of CF

34. Further Diagnostic Testing
 Genetic Testing—identify F508del mutation
 Chest CT—detect bronchiectasis and clogged airways
 Sinus CT—mucus/pus/polyps/damage
 Sputum Cultures—detects bacteria that is
characteristic to CF—Pseudomonas aeruginosa
 Fecal Elastase—measure pancreatic elastase-1

35. Testing after Diagnosis
 Imaging Tests
 Lung Function Tests
 Sputum Culture
 Organ function Tests
• Regular diabetes testing after the age of 10

36. Screening
 Prenatal Screening
• Genetic testing for parents
• Amniocentesis or chorionic villus sampling
 Newborn Screening
• Elevated IRT levels in blood

37. Treatment Options
 No cure, goal is to minimize symptoms to prevent
complications
 Accomplish this by:
• Preventing & controlling lung infections
• Loosening & removing mucus from lungs
• Preventing & treating intestinal blockage
• Providing adequate nutrition

38. Short-Term Treatment
Options
 Antibiotics to treat respiratory infection
 NSAIDs to treat fever
 Mucus-thinning drugs and bronchodilators to treat
cough, SOB
 Oral pancreatic enzymes to aid digestion

39. Long-Term Treatment
Options
 Chest Physical Therapy
• Loosens chest mucus, performed 1-4x/day
• Can be performed by someone clapping on patient’s chest
or with a chest clapper, vibrating vest, or other breathing
devices
 Pulmonary Rehabilitation
• Long-term program including nutritional counseling, exercise
training, energy conserving strategies, breathing techniques,
and psychological counseling

40. Patient & Family Education
 Screen future newborn children
 High-calorie, high-fiber, high-salt diet
 Fat-soluble vitamins
 Drink lots of fluids
 Ensure up-to-date immunizations
 Hand washing
 Exercise

41. Patient & Family Education
“The beneficial role of aerobic exercise in maintaining health
in CF has been extensively reported in previous studies. A recent
Cochrane review concluded that physical training has a positive
effect on exercise capacity, strength and lung function. Exercise
improves transepithelial potential difference in the CF airway,
improves mucus clearance, increases recruitment in lung
ventilation and enhances airway clearance. Aerobic capacity has
been related to improved survival, quality of life and professional
achievement in patients with CF. Children with CF who regularly
exercise, enjoy improved quality of life while there are also cost-
benefit implications since they require fewer antibiotics. Exercise
recommendations include various aerobic activities 3-5 times per
week for 20-45 min at intensity levels of 60-85% of maximum heart
rate depending on the severity of CF lung disease.”
-“Aerobic exercise and respiratory muscle strength in patients
with cystic fibrosis”, Theodore Dassios, Anna Katelari, Stavros
Doudounakis, Gabriel Dimitriou

42. Questions & Comments

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