Modulator |
ETI |
Lum/iva ETI |
Lum/iva |
ETI and
tez/ivaETI |
Genetics
|
F508del/R347H
|
F508del/F508del
|
F508del/F508del
|
-F508del/F508del (n=4)
-F508del/c.2921-2930ins10 (n=1)
-F508del/1066C (n=1)
-F508del/I507 (n=1)
|
Age |
12 years |
24 years |
25 years |
7 patients: Range 17-39
years |
Presentation
|
-Rash
-Serum sickness like reaction
-Fever, nausea, vomiting
-Abdominal pain, pruritic erythematous rash, targetoid lesions
-Lip swelling, joint pain, tachycardia, hypotension
-Increased inflammatory markers
|
-Rash
-Widespread, urticarial
-Back, thighs and right arm
-No systemic symptoms described
|
-History of prior catamenial hemoptysis controlled with OCPs
-Catamenial hemoptysis
|
-Testicular pain
-One reported urine more concentrated & ↑ejaculate volume
-One reported lower abdominal pain and difficulty urinating
-Several had work up: UA/BMP, Ultrasound (abdomen/testicular), abdominal
CT scan
|
Onset (timing after starting modulator)
|
5 days
|
8 days
|
-Within 1 year, not described
|
-Within 2 weeks
- 6 out of 7 occurred within 7 days
|
Treatment
|
-ETI withdrawal
-Oral corticosteroids Supportive care
|
-Oral antihistamines
-Oral corticosteroids
|
-Transitioned off OCPs
-Levonorgesterol IUD placed
-Hemoptysis continued
-Bronchoscopy showed tracheal hyperemia
-Biopsy did not show endometrial tissue
-Lesions felt to be thoracic endometriosis
-Reproductive endocrinology treated her with 6 months
leuprolide(synthetic gonadotropin releasing agent)
|
-Discontinuation of ETI in 1
-Over the counter pain medications in 3
-Antibiotics in 1 (US had shown swelling of the
scrotum)49
|
Outcome
|
-Improvement within 24 hours
-Complete resolution within 3 weeks
|
-Rash subsided within 1 week
|
-Switched to tez/iva
-Switched to OCPs
-No further hemoptysis
-2019- switched to ETI once approved
|
-All cases resolved within 3 weeks, regardless of management
methods
|
Observation
or Conclusion
|
-Long term information about potential re-initiation of ETI was not
included
|
-Safe re-initiation of ETI was possible several weeks later with
cautious titration of the dosing
|
-It was felt that lum/iva may have ↓efficacy of OCPs, ↑susceptibility to
catamenial hemoptysis due to thoracic endometriosis
|
-Only one held ETI due to the testicular pain; -ETI was able to be
slowly introduced without recurrence of pain
|