Table 3.

Detailed individual listing of AEs associated with Profhilo® 3.2% injection.

Time interval	PT demographic, country	Other suspect product	AE description & medical evaluation	Outcome
Year 1	1-F, 63 yrs, Italy	—	Edema at the injection site (zygomatic arch+suborbital area)→resulted from too hard massage after injection rather than from device itself; medical device possibly related	Topical treatment with a corticosteroid-recovering
	2-F, Italy	—	Swelling localized at the cheekbones+submalar area 20 days after the 2nd injection, followed by thickening of tissue→alternative causes, i.e., depth of injection, amount of filler administered, location of the implant, process and degree of degradation of the implant, subject's predisposition & risk factors (i.e., anatomy, prior surgery, and/or filler treatment in the area); medical device possibly related	Oral and topical steroid treatment+radiofrequency+azithromycin 500 mg for 2 wks-lost to follow-up
	3-F, Italy	—	Edema of the face + periocular area after the 2nd injection→sensitization after the 1st injection, diagnosed as an allergic reaction by the patient herself (a nurse); the reporting physician supposed that the patient had been sensitized to the product during the first injection and therefore, she suggested the occurrence of an allergic reaction during the second injection; a medical device was possibly related	4 mg Bentelan IM-resolved
	4-F, Germany		Hypertensive crisis+vertigo+wavelike nausea 5-6 hours after the injection→histamine intolerance: the patient ate fish before treatment. A reaction reoccurred after another seafood meal, not related to the MD	Resolving
Year 2	5-F, 57 yrs, Italy		Ecchymosis at the injection site with areas of telangiectasia (with no pain, no swelling, and no dermal lesions) after the 2nd injection→medical device possibly related	Topical treatment with Kelarion cream–resolved. Only few capillaries remained more visible in that area without the appearance of depressed, hardened or inflamed areas
	6-M, 54 yrs, Spain		Maculopapular erythema+itching at the injection site subsequently diagnosed as an allergic reaction-15 days after injection→pretreatment with chlorohexidine possibly causing precipitation with HA and hypersensitivity; medical device possibly related	Topical treatment with mometasone-resolved
	7-F, Germany	Botulinum neurotoxin A subcutaneous	Swelling at the injection site (lateral side of the eyes + forehead) 6 days after the injection of both products→BotToxA presumably blocked some lymphatic vessels. The medical device was not related according to both the physician and IBSA	3 ultrasound treatments-resolved
Year 3	8-F, Italy	—	Mild and transitory hematoma at the injection site→medical device possibly related	Topical treatment with arnica cream-resolving
	9-F, 59 yrs, Italy	—	Edema, intense red skin, marked hardening, mainly at the chin and malar level on the right side and nodular/granular at the cheek level→medical device possibly related	Azithromycin+deltacortene-resolved
	10-F, 40 yrs, Italy	—	Bilateral swelling more evident on the right side of the face→medical device possibly related	Ice+massage-resolved
	11-F, 54 yrs, Italy	—	Injection site reaction with redness→according to physician and IBSA, not related to Profhilo® but to patient's underlying disorder (couperose) and to the concomitant cold weather	Topical treatment with antinflammatory drug+laser-resolved
	12-F, 47 yrs, Spain		Skin eruption with redness, erythema and swelling at the injection site twice after Profhilo® injection→the physician initially considered the AE to be related to the topical application of Auriderm (vitamin K oxide) cream; however, when the same reaction occurred after the 2nd injection the causal role of Profhilo® could not be ruled out	After an AE at the 2nd injection: zamene 2 tbls (corticosteroid)-resolved

F: female; M: male; yrs: years; IM: intramuscular; wks: weeks; tbls: tablets.