Panophthalmitis in a patient with dengue fever

Abstract

Dengue fever is known for its life-threatening complications of bleeding and capillary leak syndrome. We report an unusual complication of dengue fever causing panophthalmitis, leading to rapidly progressive painful visual loss within days. Later on, the patient developed secondary bacterial infection of the eyeball and developed multiple brain abscesses due to spread of infection from the eyeball. Culture from pus swab of the right eye grew Staphylococcus epidermidis. The patient was promptly treated with broad spectrum antibiotics and after stabilisation, evisceration of the affected eye was done. Supportive therapy in the form of mechanical ventilation in view of poor sensorium, platelet transfusions for thrombocytopenia and guided fluid therapy was also provided. After multiple challenges in the management of the patient, fortunately, the patient survived but we failed to save his right eye. Therefore, it is necessary to carefully examine all vital organs at an early stage to prevent unfortunate outcome.

Background

Dengue fever is a vector borne disease transmitted by Aedes aegypti and A. albopictus mosquitoes and flourishes in the tropical and subtropical areas of the world. It is a potentially life-threatening infection because of its serious complications of severe bleeding, massive capillary leakage causing dengue shock and vital organ involvement. Eye involvement is very rare in dengue fever but has been mentioned in literature.^1–3 Here we are presenting a case that developed blindness with dengue fever due to panophthalmitis.

Case presentation

A 41-year-old Indian man presented to us during dengue season on eighth day of illness with redness and painful diminution of vision of his right eye for 2 days, and altered sensorium for 1 day. His illness started with high grade fever associated with myalgias and few episodes of vomiting for initial 5 days. He also gave a history of minor bleeding from the gums.

There was no history of persistent headache, seizures, deviation of angle of mouth, neck stiffness or diplopia. He did not have history of trauma to the eye or his head. There were no prior medical comorbidities and no significant medical or surgical history. He was a non-smoker and non-alcoholic.

On presentation, he was vitally stable. His mental status was E1 V1 M5 on the Glasgow coma scale, and he was put on mechanical ventilation for protection of his airway. On examination of his right eye, there was periorbital oedema and redness with congestion and chemosis of the conjunctiva (figure 1). The cornea appeared hazy and fundus examination and visual acuity could not be assessed. The pupillary reflex was absent on the right side. The left eye was apparently normal with preserved pupillary reflex and fundus examination was normal. There was no neck rigidity and plantar reflexes were flexor bilaterally. Rest of the examination of the chest, cardiovascular system and abdomen were within normal limits.

Figure 1.

(A) The image of the affected right eye at presentation (left image); there is eyelid oedema and redness with proptosis, conjunctival chemosis and congestion, and active pus discharge can be seen. (B) Later on, the eye became phthisical (centre image); compared with normal left eye. (C) The right eye with prosthesis, seen during follow-up visits (right image).

Investigations

In view of acute loss of vision and altered sensorium, an urgent CT scan of the head was performed which revealed a small haemorrhage in the left ganglio-capsular region with no midline shift. His platelet count was 87 x 10⁹ /L and platelet transfusions were given in view of active bleeding from gums as well as intracranial bleed. The diagnosis of dengue fever was confirmed as dengue non-structural protein-1 antigen was positive. Subsequently, he was tested for sero-conversion, and dengue IgM antibodies were found to be positive. Furthermore, testing for co-infections with malaria, scrub typhus, leptospirosis and enteric fever were found to be negative.

His sensorium improved in the further course of his stay and he was extubated successfully after 3 days. Unfortunately, after a day his sensorium deteriorated again and he was intubated for the second time. Repeat CT scan of the head revealed a new small haemorrhage in the left parietal cortex. Platelet count, platelet function testing, coagulation profile and blood pressure were normal during the second episode of intracranial haemorrhage. MRI scan of the brain and orbit was performed and it revealed multiple irregular ring enhancing lesions with coalescence in the periventricular area and dispersed all over the bilateral cerebral hemispheres (figure 2). This was suggestive of multiple intracranial abscesses. MRI of right orbit showed diffuse thickening of all three layers of the eye with enhancement, suggestive of panophthalmitis with lens dislocation in the vitreous cavity (non-traumatic).

Figure 2.

Initial MRI brain done in the first week of hospital admission. T1 weighted postgadolinium enhanced MRI brain shows multiple irregular ring enhancing lesions in both cerebral hemispheres and some of the lesions show conglomeration (red arrow), overall features are suggestive of multiple brain abscesses (left and middle image). The margins of the right eye are seen irregular with thickening of all layers with enhancement suggestive of panophthalmitis (yellow arrow; right image).

Bacterial culture from pus swab from the right eye grew Staphylococcus epidermidis and antibiotics were modified according to the sensitivity pattern. Cerebrospinal fluid studies revealed picture of pyogenic meningitis likely due to extension of the secondary eye infection; however, no organism was isolated. Immunodeficiency workup was negative for HIV, HbA1c was normal and toxoplasma serology was negative.

Differential diagnosis

Differential diagnosis of acute painful red eye includes angle closure glaucoma, conjunctivitis, keratitis, panophthalmitis and anterior uveitis. Here in our case, a classic history of fever with myalgias and thrombocytopenia in the setting of an outbreak of dengue fever lead us to believe that the eye complication in the patient was due to dengue fever and it was proven on further testing.

Differentials of multiple ring enhancing lesions included multiple brain abscesses, toxoplasmosis, neuro-cysticercosis, tuberculomas, lymphoma and metastases. Moreover, cerebral toxoplasmosis was considered a strong differential in our case because of the characteristic resemblance of the brain lesions but the patient was HIV negative and toxoplasma serology was also found to be negative.

Finally, the characteristics of the lesions were more suggestive of brain abscesses. Most importantly, prompt response to intravenous antibiotics with objective resolution of more than 60% lesions after 4 weeks of antibiotics confirmed the lesions to be brain abscesses (figure 3). The likely source of dissemination was the infected right eye as no other source could be found after extensive evaluation by ear examination, contrast-enhanced CT chest and abdomen and echocardiography. There was no underlying immunosuppressed state in the patient and he was not a known diabetic, his HbA1c value was normal.

Figure 3.

Repeat MRI brain images after 4 weeks of intravenous antibiotic therapy showing more than 60% resolution of the brain lesions as compared with previous scan (figure 2; left and middle images). Note the eviscerated right eye is replaced by prosthesis (green arrow; right image).

Treatment

Initially, the patient was managed with supportive treatment for dengue fever, with intravenous fluids, platelet transfusion and continuous vital monitoring. He required intubation and mechanical ventilation twice during the hospital stay for protection of his airway during the episodes of altered sensorium when intralesional haemorrhages occurred. He was started on broad spectrum intravenous antibiotics (meropenem and vancomycin) for the multiple intracranial abscesses and these were continued for 4 weeks. The right eye affected by panophthalmitis, later developed secondary bacterial infection and phthisis bulbi developed. It was eviscerated by the ophthalmology team, considering it to be a potential source of infection and a prosthetic implant was placed in the right orbit. Follow-up MRI brain scan was done after 4 weeks and it showed more than 60% resolution of the brain lesions by intravenous antibiotics.

Outcome and follow-up

After a challenging management, the patient improved and the evisceration surgery was uneventful. A prosthesis was inserted in place of the removed diseased eye. After completion of a 4-week course of intravenous antibiotics, the patient was discharged in a stable condition. He was followed up in our out-patient clinic and during his last visit, after about 4 weeks of discharge from hospital, the patient underwent a repeat MRI brain and it showed almost complete resolution of the brain lesions (figure 4). He is currently adjusting well socially after such a severe illness with loss of one eye and has resumed his work.

Figure 4.

MRI brain done during last follow-up visit, about 4 weeks after discharge, showing almost complete resolution of the cerebral abscesses.

Discussion

The usual presentation of dengue fever is high grade fever with myalgias and typical blanching rash on the trunk. During the critical phase of illness, few patients may develop life threatening complications like external or internal haemorrhages, capillary leak syndrome with associated shock, and various less common complications like encephalitis, aseptic meningitis and myocarditis.⁴

Eye involvement in dengue is very rare. A clinical review published in BMJ 2015 by Moreker, described dengue maculopathy as the most common ‘dengue eye disease’.¹ Other patterns of involvement include uveitis, intra-retinal haemorrhages, vasculitis, optic neuropathy, choroidal effusions, and the most dreaded of all, panophthalmitis.^{2 3} The mechanism of development of panophthalmitis is unknown. However, most likely postulated mechanism could be an immunological or inflammatory phenomenon as the complication occurred during the critical phase of the illness which is notorious for life-threatening complications.

Our observation is supported by previous few case reports; Saranappa and Sowbhagya reported a case of unilateral dengue panophthalmitis in a 6-year-old patient who also developed this complication during the critical phase of illness and developed permanent blindness of the affected eye.⁵ Another report of a unilateral panophthalmitis was reported by Richa Kamal et al who also observed the complication occurring during the critical phase of illness and Bacillus cereus was isolated from the eviscerated sample of the eye.⁶ Lastly, a case reported by Sriram et al, showed affection of both eyes by dengue panophthalmitis leading to similar outcome.⁷

We believe, the complication arose because of dysregulated immunological response which in an unclear way targeted the eye antigens and led to inflammation of all layers of the eyeball. This inflammation compromised the local immunity of the eye ball and led to invasion of secondary infection by conjunctival flora, S. epidermidis and later on, the eye succumbed and developed phthisis bulbi. To add to this complication, the infection tracked up to the brain and led to the development of multiple necrotic brain abscesses which developed intralesional bleed twice, likely due to rapidly necrotising infection. Fortunately, the complications were promptly identified and treated. After a challenging course of the illness, finally, the eye was eviscerated and also, the brain abscesses responded well to intravenous antibiotics and showed adequate resolution on repeat imaging.

Although eye involvement is rare in dengue fever, the potential should be borne in mind as it can lead to a permanent disability. Early identification of the complication and strict maintenance of local hygiene for prevention of secondary infection may potentially prevent blindness. However, treatment modalities need to be explored for saving the eye once dengue panophthalmitis sets in. Currently, the role of steroids is controversial in dengue fever and its role in this setting needs to be explored.

Patient’s perspective.

When I woke up in the hospital, I was not able to remember many things and it was a dream-like state. But gradually I realised that I was not able to see anything from right eye and there were tubes inside my mouth and nose. The doctors kept on reassuring me that everything will be fine. Soon when all tubes were out of my mouth, I could not speak properly. I do not remember most of the events clearly; only few days before going out of the hospital, I remember some things like my right eye was removed surgically because of complication of dengue fever. I also had a severe infection in my brain which got treated and I luckily came out of a serious life-threatening condition. Though I feel sad about all that happened to me and now I have only one eye for the rest of my life, I am thankful to the doctors and the Almighty that atleast my life was saved.

I wish I would have used proper precautions for prevention of dengue fever by avoiding mosquito bites by using mosquito nets or mosquito repellant liquids. Simple measures like avoiding water accumulation near homes is also an important measure to prevent breeding of mosquitoes during the rainy season.

I regret that after I developed dengue fever, I did not seek early specialist care and was not referred to a higher medical centre in time if there was suspicion of a severe illness. My eye would have been saved and maybe I would not have undergone such a tragic fate.

I believe prevention of dengue fever is more crucial than its treatment as sometimes unfortunately, things can be unpredictable.

Learning points.

• Organ involvement in severe dengue fever is common. However, eye involvement leading to blindness is rare but potentially serious.

• The symptoms of painful eye with eye discharge and swelling may herald more serious eye complications, and an urgent specialist review by ophthalmologist should be sought.

• When dengue panophthalmitis sets in, strict local hygiene of the eye should be maintained to prevent secondary infection and further complications.

• The eye complications tend to occur during the critical phase of illness and can occur even in the absence of profound thrombocytopenia.