Association of Bilateral Acute Anterior Uveitis with a Capsaicin Patch

Abstract

Purpose: To report a case of bilateral acute anterior uveitis in association with the application of an analgesic transdermal capsaicin patch.

Methods: Case report and review of literature.

Results: A 38-year-old woman suffered from bilateral acute anterior uveitis, manifesting 12–24 h after application of an analgesic capsaicin patch (Isola Capsicum N Plus) that served to alleviate muscular neck pain. Systemic immune-mediated and infectious diseases were excluded by medical history and laboratory testing. Control of inflammation was achieved with topical corticosteroid treatment within 1 week. Over the course of a 1-year follow-up, no further recurrence of uveitis was observed.

Conclusions: The case suggests a possible association of capsaicin-containing transdermal patches and acute anterior uveitis.

• Adverse effect
• analgesic patch
• capsaicin
• drug-induced acute anterior uveitis (AAU)

Capsaicin is the compound in chili peppers causing their hot taste. In medicine, topical capsaicin is used as local analgesic for the treatment of neuropathic and musculoskeletal pain. After an initial excitation of nociceptors with enhanced sensitivity (perceived as itching, pricking, or burning) and vasodilatation, a refractory period with reduced sensitivity is observed.1 Local adverse reactions with the use of topical capsaicin are quite common (up to 50%), whereas systemic adverse events (e.g., coughing) are rarely observed.1 Here, we report a case of bilateral acute uveitis after the application of a transdermal capsaicin patch.

Case Report

A Caucasian 38-year-old woman suffering from acute muscular neck pain (following heavy work as a gardener in the days before) and no positive response to systemic nonsteroidal anti-inflammatory drugs during 1 week, consecutively applied 3 halves (each one for about 12 h) of a transdermal analgesic patch (Isola Capsicum N Plus) containing capsaicin (1.5 mg/patch) and methyl salicylate (132 mg/patch). About 12–24 h after application of the first patch in her neck region, she noticed red and painful eyes and a decrease in visual acuity. Analgesic patches have consecutively been applied for a total of about 36 h, causing a mild burning sensation and discrete cutaneous redness in the area where they have been applied.

On the following day the patient presented to the Department of Ophthalmology due to increasing ocular pain and photophobia. A bilateral nongranulomatous anterior uveitis (anterior chamber cell grade 1+ to 2+) with fine keratic precipitates and a best-corrected visual acuity (BCVA) of 20/25 was found. Intraocular pressure (IOP) was unremarkable. No signs of posterior segment inflammation (e.g., vitreous cells, vasculitis) were found in clinical examination. Underlying systemic immune-mediated or infectious diseases were excluded as a result of medical history, laboratory tests, and consultation with a specialist of internal medicine/rheumatology (normal blood cell count and urine analysis; HLA-B27, HLA-B51, ANA, and TPHA negative; erythrocyte sedimentation rate, C-reactive protein, angiotensine converting enzyme, lysozyme, and antistreptolysin-O within normal range). The medical history revealed no previous episodes of red/painful eyes or any arthritis symptoms, including absence of lower back pain. A topical corticosteroid treatment with prednisolone acetate 1% eyedrops (Pred Forte) hourly and prednisolone ointment (Ultracortenol) at night was initiated, together with scopolamine 0.25% eyedrops (Scopolamin Dispersa) bid to avoid posterior synechiae. Under this treatment, uveitis resolved and recovery of visual acuity to 20/20 in both eyes was achieved within 1 week. Topical corticosteroids were tapered off within 4 weeks and mydriatics were stopped. No recurrence of uveitis or neck pain has been observed during 1 year of follow-up.

Discussion

This is the first description of uveitis in a patient in timely association with the application of a capsaicin patch. Capsaicin-induced uveitis had been described in experimental animal models. In an intraocular neurogenic inflammation model with Lewis rats, Waldrep et al. had reported a keratouveitic response after retrobulbar injection of capsaicin.2 A loss of sensory nerve function with rapid onset of inflammation within 6–12 h and a maximum of inflammatory response with leukocyte infiltration in the anterior segment after 24–48 h was observed. In a similar model, Feher et al. induced neurotrophic keratouveitis with associated peripheral vitreoretinal inflammation by retrobulbar injection of capsaicin (50 mg/kg) in young rats.3 Binding of capsaicin to transient receptor potential vanilloid type 1 (TRPV1) receptors, which is a Ca²⁺ channel of sensory nerves (present, e.g., in the cornea, conjunctiva, lacrimal glands, ciliary body, and choroid), leads to release of pro-inflammatory substance P and calcitonin gene-related peptide (CGRP) and consequently to a neurogenic inflammation; pain and heat sensation are transmitted to the brain.3,4 TRPV1 receptors have also been found in vascular endothelium, cells of the immune system (e.g., T cells and mast cells), smooth muscle cells, fibroblasts, amacrine cells, and retinal microglia cells.3

Interestingly, Feher et al. revealed a significantly attenuated inflammatory response and reduction of corneal scarring/neovascularization by additionally injecting pigment epithelium-derived factor (PEDF), a neurotrophic and anti-angiogenetic substance. They speculated that activation of TRPV1 receptors of non-neuronal cells and the subsequent release of pro-inflammatory neuropeptides like substance P and CGRP may contribute to capsaicin-induced keratouveitis.3

An epicutan capsaicin dose of 2.25 mg in our patient is not directly comparable to retrobulbar dosage (125 μg to 10 mg/eye) in the described animal models.2,3 Based on the described pathomechanisms in the animal models and after exclusion of other etiologies in our patient, a causal relationship between the capsaicin-patch application and uveitis onset may nevertheless be presumed.

As with other percutaneously applied drugs, capsaicin is thought to transfer through the skin by passive diffusion and may reach the blood circulation via the capillary plexus of the skin. It may be speculated that application in close proximity to the carotid artery has lead to rapid diffusion of capsaicin into the arterial bloodstream reaching the ciliary arteries and the nerves of the uveal tract. On the other hand, the proximity to the trigeminal nerve ganglion may have been a relevant and promoting factor. Although it may be interesting from a scientific point of view, no diagnostic reexposure to topical capsaicin has been performed in the context of achieved uveitis quiescence and of a symptom-free patient, who was reluctant to further capsaicin applications after her previous experience.

The evidence for pain treatment with (low-dose) topical capsaicin is low and local skin reactions are common,5 so there is no strong argument to support the use of topical capsaicin patches. Our case suggests an association of a bilateral acute anterior uveitis with the application of a capsaicin patch. In our patient, adequate anti-inflammatory treatment and omitting further capsaicin-patch application was sufficient to achieve quiescence and avoid further recurrences.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.