Recurrent Urticarial Vasculitis Related to Nonanimal Hyaluronic Acid Skin Filler Injection

Abstract

The author has indicated no significant interest with commercial supporters. N onpermanent biodegradable dermal fillers injections including nonanimal stabilized hyaluronic acid (NASHA) compounds have been considered to be nontoxic and nonimmunogenic implant fillers, although recent evidence shows that these statements can no longer be corroborated. Studies about localized and generalized hypersensitivity reactions, immune-mediated granulomas formation, and sarcoidosis-like disease have been published. 1À4 We report on a case of a 45-year-old woman who sought medical attention because acute urticaria and purpura appeared, possibly after Restylane (Q-Med, Uppsala, Sweden) filler was administered to correct facial wrinkles. Vasculitis was histologically confirmed afterward. A second bout of vasculitis appeared, supposedly related to a new exposure to hyaluronic acid (HA). This article analyzes the possible relationship between hyaluronic acid and NASHA (Restylane) compounds with vasculitis. The role played by contaminant proteins and cross-linking compounds related to NASHA is discussed as well. Case ReportA 45-year-old woman sought medical attention because acute urticaria and angioedema appeared after NASHA filler was administered to correct facial wrinkles. One mL of NASHA (Restylane) was placed in each nasolabial fold. Three weeks later, she noticed pruritus, urticarial lesions, and fever. She had not taken any drugs in the previous few months.Facial angioedema appeared promptly, and urticarial lesions spread through her body. A few days later, urticarial lesions became less apparent, and rash with palpable purpura in the trunk, arms, and legs appeared. Temperature was 37.61C. Mild lymphadenopathy and mild peripheral arthritis were also present. Laboratory tests disclosed a high erythrocyte sedimentation rate (50 mm); C-reactive protein, 10 mg/L (normal value o1 mg/L); alpha-2-globulin, 15%; antinuclear antibody test, 1:160 (normal value o1:40, speckled pattern); C4, 13 mg/dL (normal value 415 mg/dL). C1, C1q, C3, anti-DNA antibodies, anti-neutrophil cytoplasmic antibodies test, cryoglobulins, and anti-extractable nuclear antigen antibodies were normal or negative. Hepatitis B and C, cytomegalovirus, and Epstein-Barr virus were not found. Streptococcal antibody test (anti-streptolysin O) was negative. Anti-DNAse B was not performed. Renal function, urine sediment, and proteinuria were normal or negative. Chest X-ray and electrocardiogram recorder were also normal. Histology of a leg skin biopsy showed a typical pattern of leucocytoclastic vasculitis, with small-vessel involvement, lymphomonocytic infiltrates, and fibrin deposition. Small foci of C3 deposits in capillaries were also present. Antihistamines and prednisone (1 mg/kg per day) were begun. This treatment was successful, and angioedema, constitutional symptoms, and arthritis disappeared in a few days. Purpura cleared in less than 6 weeks. Steroids were tapered in 8 weeks. Two months later, a new bout of similar clinical charac-

Complication après injection d’acide hyaluronique : présentation d’un cas

“…Les réactions inflammatoires locales immé-diates et non allergiques (érythème, tuméfaction) sont fré-quentes (8 % des cas) : elles disparaissent sans traitement [2]. Les réactions d'hypersensibilité aiguës et graves (anaphylaxie, urticaire, angioedème) sont rares (0,6 % des cas) [6,16,17].…”

“…Pour certains auteurs, les effets indésirables des NASHA proviendraient de la composition intrinsèque du produit [16,24]. Les NASHA étant le produit d'une biosynthèse par fermentation bactérienne, il est possible que les antigènes bactériens résiduels (ils représentent moins de 1 %) soient responsables des réactions d'hypersensibilité plutôt que l'AH lui-même [16].…”

“…Les NASHA étant le produit d'une biosynthèse par fermentation bactérienne, il est possible que les antigènes bactériens résiduels (ils représentent moins de 1 %) soient responsables des réactions d'hypersensibilité plutôt que l'AH lui-même [16]. Les molécules nécessaires à la réticulation pourraient aussi être incriminées en cas de réticulation incomplète [2].…”

“…Les molécules nécessaires à la réticulation pourraient aussi être incriminées en cas de réticulation incomplète [2]. L'AH aurait également un effet pro-inflammatoire par la voie du récepteur CD44 [16].…”

“…Le Restylane Sub-Q® est un NASHA plus visqueux, plus épais et moins résorbable ; il contient 1000 particules de gel/ml [11,12]. Bien que l'AH et en particulier les NASHA soient théori-quement non-toxiques, plusieurs effets indésirables ont été rapportés [13][14][15][16].…”