Rash46 Rash47 Hemoptysis48 Testicular pain 49
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