Silicone allergy associated with intraocular silicone ball prosthesis in a dog

Abstract

A 13-year-old, male Pomeranian dog was presented for scleral rupture with intraocular hemorrhage and retinal detachment in the right eye. After intrascleral silicone ball prosthesis, recurrent swelling and granulomatous blepharitis were observed for 140 d and finally melting keratitis developed. Although an intraorbital prosthesis was implanted, recurrent, serious, erosive, and ulcerative blepharitis developed with high plasma C-reactive protein concentrations. Since the blepharitis could not be controlled, the silicone ball was removed and the affected orbit was debrided. The blepharitis resolved rapidly, and the orbit healed routinely. Positive allergic reactions to silicone were discovered through a patch test.

Key clinical message:

To the authors’ knowledge, this is the first report on silicone allergy in a dog with positive allergic reactions to silicone in the patch test.

Silicone allergy as well as latex allergy is one of the most important human medical problems associated with various medical devices (1,2), such as nasogastric tubes (3), breast implants (4), cochlear implants (5), endotracheal tubes (6), contact lenses (7), and ventriculoperitoneal tubes (8). Under contact dermatitis, this allergy is fundamentally classified as allergic contact dermatitis along with irritant contact dermatitis (1,2,9). Silicone is colorless, and polymers with siloxane (-R₂Si-O-SiR₂-), oil or rubber-like substances, and raw materials used for various medical devices. Although components of silicone occasionally induce allergic reactions with some devices routinely used in veterinary practice, there are few reports on silicone allergy and allergic contact dermatitis in animals (9,10,11). This case report deals with silicone allergy associated with intraocular silicone ball prosthesis in a dog.

Case description

An intact male Pomeranian dog (13 y, 4.8 kg) was referred to the Japan Animal Referral Medical Center for right eye exophthalmos due to trauma. The affected eye had exophthalmos with swelling, erythema, and edematous conjunctivitis, and intraocular hemorrhage (Figure 1 a). Based on negative reactions on dazzle and menace reflexes, disappearance of responses on direct and indirect pupillary light reflexes, ultrasonographic findings, and low intraocular pressure (IOP: 4 mmHg), the diagnosis was scleral rupture with intraocular hemorrhage and retinal detachment (Figure 1 b). Since no recovery of visual function was obtained, suture repair of scleral rupture and intrascleral silicone ball prosthesis (Meni-One silicone ball; Meni-One, Nagoya, Japan) with evisceration (first prosthesis) were performed on Day 7 (Figure 2, upper panel). The dog was premedicated with intravenous butorphanol tartrate (0.4 mg/kg, Vetorphale; Meiji Seika Pharma, Tokyo, Japan). Anesthesia was induced with intravenous propofol (Propofol 1% Injection 20 mL; Pfizer Japan, Tokyo, Japan), 4 to 6 mg/kg body weight (BW), and maintained with 0.5 to 2.5% isoflurane (Isoflurane TM; MSD Animal Health, Tokyo, Japan) in a mixture of 1:1 oxygen and nitrous oxide. Two suture products, braided absorbable suture (Polysorb; Covidien Japan, Tokyo, Japan) and monofilament nylon suture (Monosof; Covidien Japan) were used for internal soft tissues and skin, respectively. A multi-parameter monitor (BioScope AM130; Fukuda ME, Tokyo, Japan) was used to continuously monitor heart and respiratory rates, electrocardiogram, endo-tidal carbon dioxide concentration, arterial hemoglobin oxygen saturation, and arterial blood pressure.

Figure 1.

Appearance of the right eye and its ultrasonographic examination at first admission. Exophthalmos with erythematous, swelling, and edematous conjunctivitis were present (a). Ultrasonography revealed scleral rupture (arrow) and retinal detachment (arrowheads) (b).

Figure 2.

Clinical course of the dog. After intrascleral silicone ball prosthesis (first prosthesis) was performed on Day 7, recurrent blepharitis with swelling and granulomatous lesions developed in the right eye (a). Melting ulcerative keratitis developed (b) and an intraorbital silicone ball prosthesis (second prosthesis) was implanted. Since a severe, erosive, and ulcerative blepharitis developed (c) and plasma C-reactive protein concentrations were elevated (upper panel), the silicone ball was removed and the affected orbit was debrided.

After the prosthesis surgery, the dog had recurrent blepharitis with swelling and granulomatous lesions in the right eye by Day 140 (Figure 2 a). A melting ulcerative keratitis had developed (Figure 2 b). Therefore, enucleation and intraorbital silicone ball prosthesis (second prosthesis) were performed. Approximately 40 d after the second prosthesis, serious, erosive, and ulcerative blepharitis had developed, with extremely high plasma C-reactive protein concentrations (CRP: > 20 mg/dL) (Figures 2 c and upper panel). As this serious, recurrent blepharitis could not be controlled, removal of the silicone ball and debridement of the affected orbit were performed on Day 234. Plasma CRP concentrations rapidly decreased to the reference range and the dog completely healed (Figure 3 a,b). From Days 140 to 245, 2 recurrent skin lesions were observed in cervical skin (on Day 150, Figure 4 a) and periocular skin (on Day 234, Figure 4 b). A punch biopsy was collected from the cervical skin lesion and on histopathology, there was a necrotic area of epidermis (arrowhead) and skin appendages (broken line circle) (Figure 4 c,d). No positive result was obtained on bacterial culture of the serious blepharitis concurrent with cervical skin lesions.

Figure 3.

Appearance of the face (a) and location of the right eye socket (b) at 30 d after removal of silicone ball. Healing was satisfactory.

Figure 4.

There were 2 major skin lesions, cervical skin on Day 150 (a) (bar = 1 cm) and periocular skin on Day 234 (b) (bar = 5 mm). Hematoxylin & eosin-stained section of a biopsy from the cervical skin lesion; note the necrotic area of epidermis (arrowheads) and skin appendages (broken line circle) (c) (bar = 100 μm) and (d) (bar = 50 μm).

Although immuno-mediated causes were suspected, based on increasing CRP concentrations and histopathology of the cervical skin lesion, no positive responses were detected in antinuclear antibody (ANA) or rheumatoid factor (RF), as major markers of autoimmunity. The percentage of CC chemokine receptor 4 positive cells (CCR4⁺ cells) in cluster of differentiation 4 positive (CD4⁺) T-cells in peripheral blood was retrospectively measured in the dog; it had increased to 46.6% (reference value: < 28.7%) (12). In addition, a patch test, using a slice of silicone ball for antigen, was performed, with a clinically healthy, 2.5-year-old, intact female Pomeranian dog used as a reference for this test. Briefly, after clipping and cleaning of the dorsum skin, the test slice was applied under the patch, covered in gauze, and held in place with a bandage (13,14). At 24 h after application, erythematous and swelling lesions were observed, indicating a positive reaction (Figure 5). From these results, a definitive diagnosis of a silicone allergy was made.

Figure 5.

Patch test in this case and a reference dog. There were positive reactions, including erythema, edema, and inflammation to silicone in the case dog (a), whereas no reactions were detected in a reference dog (b).

Discussion

Silicone allergy is fundamentally classified under contact dermatitis into a category of allergic contact dermatitis, included with irritant contact dermatitis. Four types of reactions have been reported in contact dermatitis (1,5,9). Besides irritant dermatitis, as a non-immunoglobulin-E (IgE)-mediated eczematous dermatitis with non-allergic reactions, 3 other types of reactions may occur with silicone allergy. Anaphylaxis, as a serious Type I IgE-mediated hypersensitivity, develops immediately and rapidly after contact with allergens. Allergic contact urticaria, as a Type I IgE-mediated reaction, commonly develops within 10 to 15 min after contact with allergens. These 2 types of Type I IgE-mediated reactions, were also reported in silicone allergy in humans (3,6,7). Allergic contact dermatitis, as a common type of reaction and Type IV T-cell-mediated delayed type hypersensitization, develops 24 to 48 h after contact with allergens (1,2,9). Most cases of silicone allergy are Type IV delayed type hypersensitization (4,5,8). In this case, Type IV silicone allergy was suspected from the dog’s clinical course and histopathological findings of the cervical skin lesion. In allergic contact dermatitis, various degrees of histopathological lesions have been reported, e.g., perivascular dermatitis, acanthosis, spongiosis, edema, perivascular infiltration of mononuclear cells, and vasodilation probably associated with immuno-mediated disturbance of the peripheral circulation (9,15). In addition, epidermal necrosis, as detected in this case, was also common in canine allergic contact dermatitis (16,17).

In contrast, silicone allergy, manifested as allergic contact dermatitis, is extremely rare in humans and in veterinary practice. The incidence of silicone allergy was apparently not reported; however, allergic contact dermatitis was reported to be 1 to 10% of all skin diseases (1,9,10). As silicone materials have a long history of successful implantation in animals and humans, pharmacological clean conditions for manufacturing, and quality control for medical applications, few allergens related to silicone components were detected (5,6,18). In this case, something allergenic in silicone was clearly detected by the patch test (the most important diagnostic tool for identification of allergens) (18,19). In addition, population of CCR4⁺ cells in CD4⁺ T-cells in peripheral blood of this case were significantly increased, indicating activation of an allergic reaction (20,21).

The immune-mediated pathogenesis of a silicone allergy has 2 phases (9,13,22). The first phase is sensitization by a specific allergen and the second phase is elicitation of antigen-specific reactions (9,22). In the current case, intrascleral and intraorbital silicone ball prosthesis were considered to correspond to sensitization and elicitation steps, respectively. During elicitation, plasma CRP concentrations were remarkably increased. Although CRP is a nonspecific inflammatory marker, no bacterial infection was detected by bacterial culture. Serum biomarkers, such as chemokine ligand 5, adiponectin, CRP, complement factor D, were significantly increased during activation of allergic reactions (23,24). Plasma CRP concentration and population of CCR4⁺ cells in CD4⁺ T-cells might be markers for detection of allergic reactions. However, removal of the specific allergen is the most important factor to promote healing (7,9). Further study is necessary to identify the specific chemical in the silicone ball that induced the allergic reaction.

There are no reports on silicone allergy induced by medical devices in a dog, although use of an intraocular silicone ball prosthesis is common in veterinary medicine (25). To our knowledge, this is the first report on silicone allergy in a dog with positive allergic reactions confirmed with a patch test. CVJ