Severe Cocaine-Induced Midline Destructive Lesions (CIMDL) Leading to Orbital Apex Syndrome and Peripheral Ulcerative Keratitis

ABSTRACT

Purpose

To describe a case of cocaine-induced midline destructive lesions (CIMDL) associated with ocular autoimmune disease.Methods: Observational case report.

Results

A 45-year-old man with history of chronic osteolytic sinusitis due to cocaine abuse presented with sudden vision loss in right eye. Ophthalmic examination revealed fixed right mydriasis with extraocular movements limitation and optic disc swelling. Computed tomography showed an orbital infiltrating mass. The diagnosis of orbital-apex syndrome secondary to CIMDL was established. Steroids and antibiotics therapy were started without vision improvement. At 6-months follow-up, a corneal ulcer with characteristics of peripheral ulcerative keratitis (PUK) was evidenced, coinciding with an upper respiratory bacterial infection.

Conclusions

CIMDL and PUK share common pathogenic pathways, with implication of autoimmune factors and exposure to infective antigens. We hypothesized that chronic cocaine use, along with persistent bacterial infection, could have triggered an inflammatory reaction, which contributed to CIMDL development and the appearance of PUK.

KEYWORDS:

• Autoimmunity
• CIMDL
• cocaine
• orbital apex syndrome
• PUK

Cocaine use disorder represents a major public health concern. Intranasal route is the most common form of administration and may produce diverse pharmacological effects.¹ Ophthalmic adverse effects are rare, but cases of ocular surface damage, retinal vasculopathy, nasolacrimal obstruction, and orbital inflammation have been described.^2–4 Cocaine-induced midline destructive lesions (CIMDL) is a rare syndrome characterized by osseocartilaginous destruction of nose, sinuses and palate structures, and has been related with autoimmune factors.⁵ Herein we report a case of orbital apex syndrome, derived from CIMDL, associated with peripheral ulcerative keratitis (PUK).

Case report

A 45-year-old man presented with sudden vision loss in the right eye (OD), periocular pain, and purulent rhinorrhea. The patient had past history of cocaine abuse with chronic sinusopathy and septum destruction, subjected to multiple maxillofacial surgical interventions. Visual acuity (VA) in OD was hand motion. Ophthalmic examination revealed fixed right mydriasis with limitation in right ocular-motility (Figure 1) and a swollen optic disc. Computed tomography scan showed a large midline bony defect and an infiltrating mass extending into the right inferomedial orbit and apex (Figure 2a,b). The patient was admitted to hospital and was treated empirically with intravenous methylprednisolone and broad-spectrum intravenous antibiotics. Laboratory test, including complete blood count, anti-neutrophil cytoplasmic antibodies (cANCA), erythrocyte sedimentation rate (ESR), antinuclear antibodies (ANAs), and angiotensin converting enzyme (ACE) were within normal limits. Serological tests for human immunodeficiency virus, hepatitis virus, and syphilis were negative. Culture from nasopharyngeal exudate detected gram-positive cocci. Endoscopic transnasal approach with neuro-navigation system facilitated a biopsy of the right medial orbital wall (Figure 2c). The histopathologic study showed necrotizing changes, focal abscessification, and chronic inflammation (Figure 2d,e), but it did not exhibit necrotizing granulomas, typical of granulomatosis with polyangiitis (GPA), and fungal infection or mitotic figures were not identified. Drug tests were conducted with negative result and confirmed drug abstinence. The diagnosis of orbital apex syndrome secondary to cocaine abuse associated with upper respiratory tract infection was established. After tapering oral prednisone regimen and systemic antibiotic therapy, both right periorbital pain and rhinorrhea improved, but extraocular movements limitation and visual impairment persisted.

Figure 1. Motility examination reveals orthotropia in primary gaze, marked limitation in adduction, abduction, supraduction, and less in infraduction, as well as a non-reactive mydriasis of the right eye.

Figure 2. (a,b) Computed tomography scan ((a) coronal plane, (b) axial plane) shows a large midline bony defect and an infiltrating mass (blue asterisk) extending into the right inferomedial orbit and apex. It is possible to appreciate the proximity of the soft-tissue mass to the right optic nerve (red arrow). (c) Endoscopic transnasal approach for biopsy using image-guided neuro-navigation system that exhibits friable granulation tissue at the right medial orbital wall (white arrowhead), and patchy areas of necrotic tissue (white arrow). (d) Partially necrotized tissue, composed primarily of granulation tissue (hematoxylin-eosin, 100x). (e) Small vessels and fibroblastic proliferation with prominent lymphocytic and neutrophilic inflammation (hematoxylin-eosin, 200x).

Two months later, the patient reported once again right periocular pain and purulent rhinorrhea. The VA in OD worsened to light perception. The magnetic resonance imaging ruled out a cavernous sinus thrombosis, but demonstrated an enlargement of the orbital mass. Multiple biopsies from the right medial wall and periorbita were obtained once again, showing chronic inflammation, and confirmed one more time no evidence of GPA, malignancy, or fungal infection.

The patient remained stable for 6 months with close follow-up by both ophthalmology and otorhinolaryngology departments. However, in a periodic review, the patient presented with painless right red eye. Slit-lamp examination revealed a non-painful crescent-shaped corneal infiltrate with epithelial defect located at the inferior corneal pole (Figure 3a,b). Corneal sensitivity test with the tip of a cotton swab demonstrated right corneal hypoesthesia. The Schirmer’s test revealed 5 mm of Whatmann’s strip wetting in the OD and 15 mm in the left eye. Initially, a neurotrophic component was suspected and treatment with lubricant eye drops was started. Coinciding with corneal involvement, the patient was admitted for a Pseudomonas aeruginosa respiratory tract infection. Over the following days, corneal ulcer showed rapid enlargement with increasing corneal melting. Due to the concomitant corneal involvement with the systemic infectious process, corneal scraping was performed in order to rule out viral or bacterial etiologies. Microbial growth was not observed, but presence of leucocytes was detected. We considered the diagnosis of PUK, and a tapering regimen of oral steroids was initiated with highly significant improvement (Figure 3c), even if decreased corneal sensation persisted.

Figure 3. Slit-lamp biomicroscopy evaluation. (a,b) inferior peripheral crescent-shaped corneal ulcer with stromal thinning at presentation. (c) After one month of treatment, the epithelial defect was healed.

Discussion

CIMDL is a rare complication of cocaine nasal inhalation and its prognosis is usually poor. Some conditions such as infections, lymphoid or hematological tumors, and immunological diseases like GPA may mimic CIMDL. These entities are potentially life-threatening, and could be misdiagnosed in patients with history of long-term intranasal cocaine use.⁶

Inhaled cocaine may provoke necrosis of cartilage and mucosa, as well as impairment of the physiological defense mechanisms inside the nasal cavity, leading to chronic bacterial carriage and contributing to CIMDL development. Bacterial superinfection has been documented in patients with CIMDL, and could produce an enhancement of the inflammatory process, in spite of drug abstinence, as occurred in our patient.^7–9

Infrequently, CIMDL expansion may result in orbital invasion leading to an orbital apex syndrome.¹⁰ It is a complex clinical disorder featuring visual loss from optic neuropathy and ophthalmoplegia, affecting multiple cranial nerves. There are few reports of orbital apex syndrome associated with intranasal cocaine abuse,^11,12 and we therefore considered the inclusion of CIMDL as part of the differential diagnosis. The distinction with cavernous sinus syndrome might be challenging, and the main differentiator can be the presence of neuropathy in orbital apex syndrome.¹³ Indeed, the exact mechanisms of optic nerve damage remain unclear, but a combination of compressive, infiltrative and ischemic pathways have been proposed.^9,10,12

On the other hand, we hypothesized that corneal hypoesthesia would also be a complication of orbital apex syndrome. Impairment of trigeminal corneal innervation at any point of its course may lead to decrease of corneal sensation and subsequent neurotrophic keratitis (NK).^14,15 In our patient, we initially considered the diagnosis of NK due to the result of corneal sensitivity test. The relevant right shortening of Schirmer test would also suggest a reduced corneal sensation, as the lacrimal gland function is influenced by sensory nerves. Nonetheless, the morphologic features of the corneal ulcer with presence of leucocytes, and the appropriate response to corticosteroids therapy, led us to the diagnosis of PUK.

PUK is a form of ocular inflammation that involves the outer portions of the cornea and it is frequently associated with systemic conditions, like ANCA-associated vasculitides.^16,17 It is known that the peripheral cornea holds anatomic and physiologic characteristics that predispose it to inflammatory reactions with immune complexes deposition.^18,19 In this way, ANCA formation with stimulation of cytokines and collagenases release can contribute to keratolysis.^20,21 Furthermore, hypersensitivity reaction against exogenous triggers, like bacterial antigens, could also have an influence on corneal stromal inflammation,^16,22,23 which would be consistent with the concomitant bacterial infection presented by our patient.

Interestingly, it is increasingly recognized that cocaine and levamisole, a common adulterant of cocaine, have been implicated as triggering factors of ANCA development with multiorgan involvement.^24–26 The perinuclear staining pattern of ANCA (pANCA) predominates in CIMDL, whereas the cytoplasmic pattern (cANCA) is more frequent in GPA. The prevailing pANCA type is directed against human neutrophil elastase (HNE), and it is not frequently detected in other autoimmune diseases, so it can be used to distinguish CIMDL between other entities.^27–29 Unfortunately, our center did not have access to the HNE assay, which is not broadly available.

At this point, it is interesting to highlight the study conducted by Trimarchi et al., which suggested that CIMDL seems to be the result of an inflammatory tissue response triggered by cocaine use, with the participation of infective agents, in patients predisposed to autoimmunity.³⁰ These findings could explain the low prevalence of CIMDL among cocaine users, and its previously reported association with other immune diseases.^31,32

For all these reasons, we hypothesized that chronic cocaine use, along with persistent bacterial infection, could have triggered an inflammatory reaction, which contributed to CIMDL development and the appearance of PUK.

To the best of our knowledge, this is the first case of orbital apex syndrome with optic neuropathy and corneal hypoesthesia in the presence of CIMDL, complicated with an ocular autoimmune condition.

Declaration of interest

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