Rare Case of Intraocular Jarisch-Herxheimer reaction induced by Lemierre Syndrome antibiotherapy
Lemierre syndrome (LS) is defined as septic thrombosis of the internal jugular vein, secondary to an acute otolaryngologic infection, resulting in metastatic septic complications. This syndrome is classically associated with Fusobacterium spp., which is an anaerobic gram-negative bacillus commonly found in the oropharynx, gastrointestinal tract, and female genital tract and well known for its thrombogenic nature.
The Jarisch–Herxheimer reaction (JHR) is characterized by an acute inflammatory response induced by the sudden release of endotoxin-like material (lipoprotein) from spirochetes and the elevation of cytokines (TNF-a, IL-6 and IL-8), after penicillin administration. The JHR occurs during the first days of antibiotics treatment and causes a flare-up of pre-existing conditions, including fever, chills, headache, and myalgias.
Prithvi Ramtohul, Céline Boulicot-Seguin, and Caroline Marc described a single case of an isolated intraocular JHR associated with LS and proposed pathophysiologic mechanisms.
CASE REPORT
A previously healthy 43-year-old-man, with no significant medical history or medications, presented with a 7-day history of severe sore throat, malaise, and fever. Empiric treatment was initiated by his family doctor with oral amoxicillin–clavulanic acid 3 g per day. Despite this regimen, his condition worsened, and he was admitted to the hospital 5 days later with dyspnea, trismus, and severe sepsis.
On physical examination, the left tonsil was considerably enlarged and enflamed. Left submandibular lymph nodes were swollen and highly tender.
The enhanced computed tomography revealed bilateral phlegmonous tonsillitis, predominantly left-sided, complicated with left septic internal jugular vein thrombosis, cervical cellulitis and lymphadenitis. There was no evidence of septic emboli arising from the left internal jugular vein and affecting distant sites, particularly lungs, brain, and eyes were unremarkable.
Complete blood analysis was significant for leukocytosis (26,500 cells per microliter with 85% neutrophils) and elevated C-reactive protein (87 mg/dL). Two blood cultures were reported positive for gram-negative anaerobic bacilli, subsequently identified as Fusobacterium necrophorum. Therefore, the diagnosis of LS was confirmed, and the patient was treated with high-dose parenteral antibiotics (piperacillin– tazobactam 12 g per day).
He complained of blurred vision in both eyes few days later. The best-corrected visual acuity (BCVA) was 20/32 in both eyes. Intraocular pressure was 12 mmHg in both eyes. The anterior segment examination was normal, especially no anterior chamber inflammation was noted. Both pupils were equal and reactive to light and accommodation. Funduscopic examination disclosed bilateral cystoid macular edema (CME), associated with mild peripheral retinal vasculitis (diffuse and segmental perivascular sheathing in the temporal quadrant). Detailed observation of the vitreous was normal. Spectral domain optical coherence tomography confirmed the CME in both eyes.
In the early phase, fluorescein angiography (FA) showed no marked prolongation of the arm-to-retina and retinal circulation time. Peripheral diffuse capillary leakage was bilaterally noted, with diffuse pinpoint areas. Late phase of FA demonstrated bilateral perifoveal leakage forming the classic petaloid leakage pattern and small optic disk swelling. There was no evidence of retinal ischemia or neovascularization.
According to the chronology and these imaging findings, an intraocular JHR was suspected. However, the use of systemic steroid therapy, as it is classically recommended in JHR, was prohibited by severe unstable hypertension (blood pressure of over 160/100 under tritherapy). Therefore, close observation was first decided. After 1 month, as there was no improvement in CME (central macular thickness: 537 mm, in the right eye/479 mm, in the left eye) and BCVA (20/32 in both eyes), authors performed a single intravitreal injection of ranibizumab 0.5 mg (0.05 mL) in both eyes.
One month after injection, authors noted a remarkable resolution of the CME (central macular thickness: 235 mm, in the right eye/232 mm, in the left eye), and the BCVA increased to 20/20 in both eyes. Follow-up FA findings were also relevant, as previous described lesions entirely regressed. The result of this single intravitreal injection of ranibizumab was sustained; BCVA remained unchanged (20/20 in both eyes), and no recurrence of CME or retinal vasculitis was found after 4-year follow-up.
Lemierre syndrome is a potentially fatal condition that may complicate an acute oropharyngeal infection in an otherwise healthy individual. The classical criteria are as follows: evidence of pharyngeal infection with anaerobic bacteria, bacteremia with positive blood culture, and septic thrombosis with involvement of the internal jugular vein, resulting in metastatic septic emboli.
Ophthalmic involvement in LS is rare with an incidence rate of 5%, including endogenous endophthalmitis, vitreous hemorrhage, anterior uveitis, proptosis, orbitopathy, and isolated fourth and sixth nerve palsies. In isolated intraocular JHR, vision impairment classically occurs within 1 to 4 days after initiation of antibiotic treatment. In this report, authors considered that the retinal involvement was probably the result of a JHR because of its close relation to the antibiotics onset.
Ranibizumab is a humanized monoclonal antibody fragment produced in Escherichia coli cells by standard recombinant DNA technology and is targeted against human vascular endothelial growth factor A (VEGF-A). Its common indications are wet age-related macular degeneration, diabetic macular edema, and macular edema after retinal vein occlusion. Plasma concentrations of cytokines (TNF-a, IL6, and IL-8) were measured deeply increased in patients experiencing a JHR in relapsing fever. VEGF is a major regulator of angiogenesis and vascular permeability and is highly involved in the development of uveitic macular edema of various origins. Intravitreal injection of ranibizumab could be an alternative when systemic steroid therapy is contraindicated, such as unbalanced diabetes, active or latent infections, severe hypertension, and unstable mental disorders.
In this case, a single intravitreal injection was required without any recurrence after a 4-year follow-up. Although, anti-VEGF therapy has a restricted duration effect, the absence of relapse may be explained by the self-limited nature of JHR. In conclusion, authors reported the first case of isolated intraocular JHR induced by LS antibiotherapy and successfully treated with a single intravitreal injection of ranibizumab.
Source: Prithvi Ramtohul, Céline Boulicot-Seguin, Caroline Marc; 2021, Retinal Cases & Brief Reports 15: 4
