Ophthalmic manifestations of arbovirus infections in adults

ARTICLE IN PRESS a r c h s o c e s p o f t a l m o l . 2 0 1 9;x x x(x x):xxx–xxx

ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia

Original article

Ophthalmic manifestations of arbovirus infections in adults夽 L. Del Carpio-Orantes a,∗ , E.R. Contreras-Sánchez b , R.I. Luna-Ceballos c a

Departamento de Medicina Interna, Hospital General de Zona 71, Delegación Veracruz Norte, Instituto Mexicano del Seguro Social, Mexico b Unidad de Medicina Familiar 61, Delegación Veracruz Norte, Instituto Mexicano del Seguro Social, Mexico c Coordinación de Investigación en Salud, Delegación Veracruz Norte, Instituto Mexicano del Seguro Social, Mexico

a r t i c l e

i n f o

a b s t r a c t

Article history:

Introduction and objectives: Emerging arbovirus infections have classic symptoms such as

Received 11 April 2019

fever, arthralgia, or rash. As some of them have ophthalmic symptoms/signs, the main

Accepted 16 September 2019

objective is to evaluate whether these help clarify the clinical diagnosis.

Available online xxx

Material and methods: A descriptive and retrospective study was conducted, in which cases of adults who attended an evaluation in 2016. The general and ophthalmic symptoms were

Keywords:

analysed on those meeting the definition of dengue, Zika, and chikungunya.

Zika

Results: A total of 10,327 cases of arbovirosis were recorded, of which 5388 (52.2 %)

Dengue

were Dengue, 3529 (34.1 %) Zika, and 1410 (13.6 %) were Chikungunya. The main symp-

Chikungunya

toms and signs of Dengue were: fever, headache/retro-orbital pain, arthralgia, rash, and

Conjunctivitis

nausea/vomiting. For Zika cases they were: exanthema, swollen glands, headache, arthral-

Uveitis

gia, and conjunctivitis, and for Chikungunya cases: rash, fever, arthritis, headache, and

Episcleritis

nausea/vomiting. The group with the most ophthalmic signs/symptoms was Zika, predom-

Epiphora

inantly non-purulent conjunctivitis and retro-orbital pain, epiphora, episcleritis, anterior

Cranial nerve palsy

uveitis, as well as neurological syndromes such as isolated cranial nerve palsy (III and IV) or Miller Fisher syndrome. Conclusions: Ophthalmic signs/symptoms of Zika infection can help the clinical diagnosis of these arbovirosis. ˜ ˜ S.L.U. All rights © 2019 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana, reserved.

夽 Please cite this article as: Del Carpio-Orantes L, Contreras-Sánchez ER, Luna-Ceballos RI. Manifestaciones oftálmicas de las infecciones arbovirales en adultos. Arch Soc Esp Oftalmol. 2019. https://doi.org/10.1016/j.oftal.2019.09.009 ∗ Corresponding author. E-mail address: [email protected] (L. Del Carpio-Orantes). ˜ ˜ S.L.U. All rights reserved. 2173-5794/© 2019 Sociedad Espanola de Oftalmolog´ıa. Published by Elsevier Espana,

OFTALE-1572; No. of Pages 4

ARTICLE IN PRESS 2

a r c h s o c e s p o f t a l m o l . 2 0 1 9;x x x(x x):xxx–xxx

Manifestaciones oftálmicas de las infecciones arbovirales en adultos r e s u m e n Palabras clave:

Introducción y objetivos: Las infecciones por arbovirus emergentes tienen síntomas clási-

Zika

cos como fiebre, artralgias o rash, dado que algunas tienen síntomas/signos oftálmicos, el

Dengue

objetivo central es evaluar si estos ayudan a esclarecer el diagnóstico clínico.

Chikungunya

Material y métodos: Estudio descriptivo y retrospectivo, se analizan los casos de adultos

Conjuntivitis

que acudieron a evaluación en 2016, cumpliendo la definición de caso de dengue, zika y

Uveitis

chikungunya, se analiza la sintomatología general y la oftálmica.

Epiescleritis

Resultados: Se registró un total de 10,327 casos de arbovirosis, de las cuales 5388 fueron

Epifora

Dengue (52.2 %), 3529 Zika (34.1 %) y 1410 Chikungunya (13.6 %); los principales sín-

Parálisis de nervios craneales

tomas y signos de Dengue fueron: fiebre, cefalea/dolor retroorbitario, artralgias, exantema y náuseas/vómito; para los casos de Zika: exantema, adenomegalias, cefalea, artralgias y conjuntivitis; para los casos de Chikungunya: exantema, fiebre, artritis, cefalea y nauseas/vómito. El grupo con más signos/síntomas oftálmicos es el de Zika, predominando conjuntivitis no purulenta y dolor retroorbitario, epífora, epiescleritis, uveitis anterior, hasta síndromes neurológicos como parálisis aisladas de pares craneales (III y IV) o síndrome de Miller Fisher. Conclusiones: Los signos/síntomas oftálmicos de la infección por zika pueden ayudar al diagnóstico clínico entra estas arbovirosis. ˜ ˜ S.L.U. Todos de Oftalmolog´ıa. Publicado por Elsevier Espana, © 2019 Sociedad Espanola los derechos reservados.

Introduction Arboviral diseases exhibit high incidence and prevalence in the authors’ country, categorized as an endemic area. After the arrival of chikungunya and zika to the American continent, published reports increased together with the incidence of neurological syndromes such as the Guillain-Barré and the congenital Zika syndromes, mainly due to zika, regarded as a quintessential neurotrophic virus.1,2 Due to the clinical symptoms of said diseases, it is difficult to differentiate one from another except for characteristic peculiarities, i.e., chikungunya mainly compromises joints, dengue exhibits a preference for vascular endothelium giving rise to major hematological alterations while zika ranges from asymptomatic presentations without fever to the abovementioned neurological syndromes. Ophthalmological or oculomotor compromise has been reported for the 3 main arboviral infections. Dengue can produce variable ocular compromises ranging from conjunctivitis, retro-orbital pain, vitreous and retinal hemorrhage, foveolitis and dengue maculopathy, with isolated cases being abundantly reported in the literature.3 Chikungunya infection acutely compromises the ocular apparatus by means of conjunctivitis, photophobia and retro-orbital pain (typical expressions of all arbovirosis). Less frequently keratitis, anterior uveitis, episcleritis and Fuchs heterochromic iridociclitis have been reported. Posterior segment impairments include retinitis, choroiditis, optical neuritis and neuro-retinitis. The latter have been associated to slight vitritis, retinal hemorrhage, retinal edema and

posterior pole vascular compromise. Other findings include bilateral outer ophthalmoplegia, incongruous homonymous hemianopsies, central retinal artery occlusion, serous retinal detachments, multifocal choroiditis and vi pair palsy. All the above leads to suspect a neurotrophic as well as arthritogenic nature of the chikungunya virus. Lastly, oculomotor impairment due to zika virus expresses mainly through conjunctivitis, one of the clinical criteria for diagnosis. However, microcephaly exhibited by newborns has associated other congenital alterations, including ophthalmic alterations, in a percentage ranging between 21.4 and 55 %, with essential posterior segment damage including retina, retinal vessels and optic nerve being reported. Some authors have reported coloboma, lens subluxation, cataracts, glaucoma, strabismus, nystagmus and microphthalmia, while other series reported chorioretinal atrophy, retinal pigmentation changes, optic nerve hypoplasia, optic disc paleness, increased optic disc curvature, hemorrhagic retinopathy and abnormal retinal vasculature. Retinal dotted pigment and chorioretinal atrophy has been reported at the retinal level. In addition to non-purulent conjunctivitis that constitutes one of the main diagnostic signs in adult patients, reports include anterior and posterior uveitis, hypertensive iridocyclitis and unilateral acute maculopathy among others.4–10 All arboviral infections could involve ophthalmic impairment due to neurotrophic mechanisms (colonization starting from the central nervous system through the chiasma and optic nerve) and low immune response in the oculomotor apparatus, making the latter more susceptible to become a preferred location for said viruses.

ARTICLE IN PRESS 3

a r c h s o c e s p o f t a l m o l . 2 0 1 9;x x x(x x):xxx–xxx

Table 1 – Most frequent clinic expressions (general signs and symptoms). Dengue Total number of cases Fever Headache Conjunctivitis Arthralgia/polyarthralgia Exanthema Arthritis Petechia Adenomegalia Nausea/vomits Diarrhea Hemorrhages Hepato/splenomegaly Jaundice Tourniquet Respiratory symptoms Cardiac symptoms Neurological symptoms

5388 5384 (99.9 %) 5060 (93.9 %) 20 (0.3 %) 4779 (88.6 %) 4.110 (76.2 %) 137 (2.5 %) 305 (5.6 %) 243 (4.5 %) 1.800 (33.4 %) 278 (5.1 %) 15 (0.2 %, digestive) 2 (hypermenorrea) 13/0 1 23 (0.4 %) 6 (dyspnea) 58 (1.07 %, cough) 3 (palpitations) 2 (angina) 4 (lethargy)

Zika

Chikungunya

3529 2362 (66.9 %) 3031 (85.8 %) 2941 (83.3 %) 2952 (83.6 %) 3500 (99.1 %) 80 (2.2 %) 43 (1.2 %) 3217 (91.1 %) 1100 (31.1 %) 221 (6.2 %) 4 (digestive)

1410 1409 (99.9 %) 1344 (95.3 %) 151 (10.7 %) 1386 (98.2 %) 1410 (100 %) 226 (16 %) 57 (4.04 %) 60 (4.25 %) 723 (51.2 %) 94 (6.3 %) 0

3/8 3 3 3 (tos)

4/6 4 1 0

3 (palpitations)

4 (palpitations)

1 (disorientation) 4 (convulsions)

4 (disorientation) 4 (convulsions) 4 (lethargy)

Symptoms with higher incidence shown in bold type.

Methods A descriptive and retrospective study analyzing adult ambulatory patients who visited due to suspected arbovirosis from vector transmission between January and December 2016 in the Veracruz Norte section of the Social Insurance Institute of Mexico. The cases were classified in accordance with the operational definition of suspected dengue, chikungunya and zika. The main and general symptoms were analyzed together with ophthalmological symptoms exhibited by each arboviral group.

Results Up to 2016, the Veracruz Norte section of the Social Insurance Institute of Mexico registered 10,327 cases of arbovirosis, of which 5388 fulfilled the operational definition of dengue (52.2 %), 3529 cases for zika (34.1 %) and 1410 cases for chikungunya (13.6 %). For all 3 arbovirosis, the most affected age group was 21–30 years. The most affected sex for dengue was female with 3032 cases (56.27 %). In contrast, for zika and chikungunya the most affected sex was male, with 2375 cases (67.29 %) and 941 cases (66.7 %), respectively. In what concerns symptomatology, the main symptoms and signs exhibited by dengue cases were fever, headache/retro-orbital pain, arthralgia, exanthema and nausea/vomiting, while for zika the main symptoms were exanthema, adenomegalias, headaches, arthralgia and conjunctivitis. For chikungunya the main symptoms were exanthema, fever, arthritis, headaches and nausea/vomit (Table 1). The main ophthalmological expressions were exhibited by the zika group with the broadest range of symptoms

from non-purulent conjunctivitis and retro-orbital pain to neurological syndromes associated with ophthalmic motor alterations involving isolated palsy of oculomotor cranial pairs (iii and iv) or Miller Fisher syndrome cases which come from the manifest neurotrophism of the zika virus. In smaller but equally severe proportions, anterior uveitis and episcleritis cases were reported as well as one case of amaurosis fugax, which was discarded as associated to retinal or optic nerve impairment. In addition, minor signs included blepharitis, epiphora and photophobia (Table 2). In contrast, the main ophthalmic expression in dengue was retro-orbital pain (which is included in the suspect case definition) followed by photophobia and a few cases of non-purulent conjunctivitis. Lastly, chikungunya is the arboviral infection with the lowest ophthalmic impairment, non-purulent conjunctivitis cases in smaller proportion compared to the other arbovirosis.

Conclusions In summary, a patient with suspected arboviral infection in an endemic region exhibiting significant ophthalmic impairment has a higher probability of suspected zika virus infection than the other arbovirus included in the study. Despite the multiple reports of dengue and chikungunya cases with ocular impairment, the present series did not identify posterior segment or neuro-ophthalmic compromise, with retro-orbital pain being more relevant in dengue (which is part of the suspect case definition) and photophobia. Impairment caused by chikungunya is minimal compared to the other arboviral infections. The most significant oculomotor apparatus compromise is related to viral neurotrophism associated to other acute neurological syndromes, in addition to the preference for ocular

ARTICLE IN PRESS 4

a r c h s o c e s p o f t a l m o l . 2 0 1 9;x x x(x x):xxx–xxx

Table 2 – Main ophthalmic expression in adults with arboviral infections.

Cases (n) Non-purulent conjunctivitis Retro-orbital pain Photophobia Episcleritis Anterior uveitis Blepharitis Epíphora Amaurosis fugax Ophthalmoplegia (iii pair) Ophthalmoplegia (iv pair) Ophthalmoplegia, ataxia and arreflexia (Miller Fisher syndrome)

Dengue

Zika

5.388 20 (0.4 %) 4.105 (76 %) 1.370 (25 %) 0 0 0 0 0 0 0 0

3.529 2.941 (83 %) 355 (10 %) 55 (1.55 %) 260 (7 %) 5 (0.14 %) 20 (0.5 %) 38 (1 %) 1 (0.02 %) 3 (0.08 %) 1 (0.02 %) 5 (0.14 %)

Chikungunya 1.410 151 (10.7 %) 0 0 0 0 0 0 0 0 0 0

Symptoms with higher incidence shown in bold type.

mucosa (the presence of the zika virus has been demonstrated in conjunctival mucosa smears during the first 7 days of the infection) and its increased persistence in ocular fluids such as tears. In fact, viral presence has been demonstrated up to 30 days after acute onset and could be considered as a source of infection.11 Lastly, ocular apparatus compromise in a patient with suspected arboviral infection should lead to suspecting the zika virus until demonstrated otherwise.

Conflict of interests No conflict of interests was declared by the authors.

references

1. Del Carpio-Orantes L. [Emerging Arboviroses in Mexico: chikunguna and zika]. Revista médica del Instituto Mexicano del Seguro Social. 2015;54:278–9. 2. Del Carpio-Orantes L. Zika, a neurotropic virus? Revista ´ medica del Instituto Mexicano del Seguro Social. 2016;54(4):540.

3. Del Carpio-Orantes L. Dengue for apparatus and systems. MEDtube Sci. 2015;(III):21–4. 4. Arrieta B, Saldarriaga C. Manifestaciones oculares de ˜ Revisión de Literatura. infección del virus del Chikunguna: Rev Soc Colomb Oftalmol. 2015;48:206–12. 5. Mahendradas P, Avadhani K, Shetty R. Chikungunya and the eye: a review. J Ophthalmic Infl amm Infect. 2013;3:35. 6. Miranda Hernández I, Río Torres M. Impacto de la infección por virus ZIKA en Oftalmología. Revista Cubana de Oftalmología. 2016;30 http://www.revoftalmologia.sld.cu/index.php/oftalmologia/ article/view/502 7. Jampol LM, Goldstein DA. Zika virus infection and the eye. JAMA Ophthalmol. 2016;134:535–6. 8. Ventura CV [citado 2 de enero de 2017]. Disponible en: http://jamanetwork.com/journals/jamaophthalmology/ fullarticle/2525773, 2016. 9. Del Carpio-Orantes L. Congenital Zika syndrome, time to communicate experiences. J Maternal-Fetal Neonatal Med. 2018, http://dx.doi.org/10.1080/14767058.2018.1465916. 10. Del Carpio-Orantes L, González Clemente MC. Microcefalia y arbovirus. Rev Med Inst Mex Seguro Soc. 2018;56:186–8. 11. Tan JJL, Balne PK, Leo YS, Tong L, Ng LFP, Agrawal R. Persistence of Zika virus in conjunctival fluid of convalescence patients. Sci. Rep. 2017;7:11194, http://dx.doi.org/10.1038/s41598-017-09479-5.