COVID-19-Related Chronic Bilateral Dacryoadenitis: A Clinicopathological Study.

IMPORTANCE: Pathological features of ophthalmic aftereffects of COVID-19 are important for new insight in treating patients. OBJECTIVE: To examine the expression of SARS-CoV-2 nucleocapsid protein and angiotensin-converting enzyme 2 (ACE2) in lacrimal gland tissues of a patient with COVID-19 and a patient without COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective case-control study, the case of a 35-year-old woman with positive test results for SARS-CoV-2 who had had lacrimal gland enlargements for 6 months was analyzed. A 43-year-old woman without COVID-19 who had idiopathic chronic bilateral dacryoadenitis served as a negative control. MAIN OUTCOMES AND MEASURES: Histopathology and immunohistochemistry with anti-SARS-CoV-2 nucleocapsid protein and ACE2 in the lacrimal glands. RESULTS: Both patients were Japanese women aged 35 years (case) and 43 years (control). Histopathologic findings in the patient with COVID-19 demonstrated marked inflammatory cell infiltration, lymphoid follicles, and germinal center formation in the lacrimal gland. The inflammation was mainly made up of lymphocytes and plasma cells with several polymorphonuclear leukocytes, where the lacrimal glands were atrophic. Of note, a number of lacrimal gland ducts markedly contained eosinophilic materials in the lumens, which indicated glandular damage. Immunoreactivity for SARS-CoV-2 nucleocapsid protein was noted in the inflammatory cells around the lacrimal gland ductal epithelia. In addition, strong ACE2 expression was noted in the lacrimal gland. In the patient without COVID-19, marked inflammation was noted in the lacrimal gland; however, there were no eosinophilic material deposits in the ductal lumens. SARS-CoV-2 nucleocapsid protein immunoreactivity was not observed, whereas ACE2 was expressed in the lacrimal glands. CONCLUSIONS AND RELEVANCE: In this case-control study, expression of ACE2 indicated that the lacrimal gland could be a target organ for SARS-CoV-2 to adhere to. Chronic bilateral dacryoadenitis in the patient with COVID-19 showed SARS-CoV-2-positive inflammatory cells with glandular damage, which might be a COVID-19-associated ophthalmic aftereffect.

Síndrome de retención aguda lagrimal asociada a infección por virus de Epstein-Barr / Acute dacryocystitis retention syndrome due to Epstein-Barr virus

Varón de 4 años, sin antecedentes de obstrucción de vía lagrimal, que acude con una masa dolorosa en el canto interno del ojo izquierdo y febrícula de 3 días de evolución, sin mejoría con antibióticos orales por lo que se ingresa para estudio y tratamiento. En la exploración presenta edema palpebral con hiperemia periocular, dolor a la palpación del saco y exudado amigdalar. Se administran antibióticos por vía intravenosa. Tras 4 días de ingreso, el cuadro lagrimal mejora, empeorando el estado general con aparición de adenopatías cervicales. La tomografía computarizada órbito-cervical refleja un aumento del tamaño del saco lagrimal izquierdo compatible con dacriocistitis aguda y adenopatías cervicales. Serología y PCR positivas a virus de Epstein-Barr (VEB). Es dado de alta por resolución del cuadro a los 8 días con antibioterapia por vía oral. Se diagnostica de síndrome de retención aguda lagrimal asociado a VEB. A los 6 meses, continúa asintomático sin lagrimeo (AU)

A 4 year-old boy with no previous history of eye or nasolacrimal disease was referred due to a painful mass on his left inner canthus, of 3days onset, with no improvement in spite of oral antibiotics. On examination eyelid oedema with periocular hyperaemia was noted. Lacrimal sac palpation was painful and tonsillar exudation was reported. He was admitted and started on intravenous antibiotics. Four days later, lacrimal signs started to improve, but his general condition become worse. Head and neck computed tomography scan showed a left lacrimal sac enlargement, suggestive of acute dacryocystitis and swollen laterocervical lymph nodes. Epstein Barr virus (EBV) serology and PCR testing were positive. The child responded well after 8days, and was discharged with oral antibiotics. Acute dacryocystic retention associated with EBV was suspected. Six months later, the patient remained asymptomatic with no tearing or other lacrimal symptoms (AU)

Development of lacrimal gland inflammation in the mouse model of herpes stromal keratitis.

Herpes stromal keratitis (HSK) is a chronic immunoinflammatory condition which develops in response to recurrent herpes simplex virus-1 (HSV-1) infection of the cornea. Patients with HSK often demonstrate the concurrence of corneal desiccation and the loss of blink reflex. However, the relationship between severity of HSK, level of basal tears and inflammation of the lacrimal gland is mostly unexplored. In this study, we compared these variables in extraorbital lacrimal gland (EoLG) after corneal HSV-1 infection in the C57BL/6J mouse model. Our results showed a significant reduction in the volume of tears in infected eyes during the development of HSK. Extensive architectural damage to EoLG, presumably caused by a massive influx of interferon-gamma secreting T cells, was observed during clinical disease period of HSK. A positive correlation between the decrease in tear volume, severity of HSK and the damage to EoLG were evident in infected mice. The presence of infectious virus measured in EoLG during pre-clinical, but not clinical disease period of HSK, suggested that viral cytopathic effects are not the major contributors of extensive damage seen in EoLG. Furthermore, topical administration of lacritin peptide delayed but did not prevent the decrease in tears in HSV-1 infected mice, and had no significant effect in either reducing the severity of HSK or T cell infiltration in EoLG of infected mice. Together, our results showed an interplay between the severity of HSK, inflammation of EoLG, and the reduced level of tears after corneal HSV-1 infection.

[Acute dacryocystitis complicating primary mononucleosis infection]. / Dacryocystite aiguë sur une primo-infection mononucléosique.

INTRODUCTION: Infectious mononucleosis may lead to numerous complications. Tonsillar hyperplasia with risk of airway obstruction is well known. Dacryocystitis is a rare but potentially severe complication. OBSERVATION: A 6-year-old child with primary mononucleosis infectious diagnosed 8 days before, developed acute dacryocystitis, with rapid evolution to orbital cellulitis, despite adequate antibiotherapy. Emergency surgical drainage was required. DISCUSSION: Dacryocystitis is a rare and little documented complication of EBV infection. Its acute evolution to orbital cellulitis is possible and potentially severe. Its physiopathology is specific. Patients are initially free of chronic stenosis and epiphora, which express acute obstruction of the lachrymal sac due to general lymphoid hyperplasia.

Dacrioadenite bilateral causada pelo vírus Epstein-Barr: relato de caso / Epstein-Barr virus bilateral dacryoadenitis: case report

Os autores apresentam um caso raro de dacrioadenite aguda bilateral associada à mononucleose. Paciente do sexo feminino, 27 anos, tinha aumento agudo da glândula lacrimal, bilateral, com sinais flogísticos. As alterações tomográficas e laboratoriais confirmaram o diagnóstico e o tratamento com esteróide sistêmico foi introduzido, com resolução completa dos sinais e sintomas. COMENTÁRIOS: A dacrioadenite é uma apresentação incomum da mononucleose infecciosa e pode minimizar outras manifestações desta doença. O diagnóstico de mononucleose deve ser considerado em casos de dacrioadenite aguda bilateral. Os esteróides sistêmicos contribuem para a resolução do quadro inflamatório.

The authors present a rare case of acute bilateral dacryoadenitis in association with infectious mononucleosis. A 27 year-old woman had acute bilateral lacrimal gland enlargement with inflammatory signs. The CT scan findings and laboratorial investigations confirmed the diagnosis of infectious mononucleosis. The systemic treatment with intravenous steroids was initiated leading to complete remission of the signs and symptoms. COMMENTS: Dacryoadenitis is an uncommon manifestation of infectious mononucleosis and may minimize other signs of the disease. Mononucleosis has to be considered in acute dacryoadenitis cases. Systemic steroids contribute to the fast regression of inflammatory condition.

[Epstein-Barr virus bilateral dacryoadenitis: case report]. / Dacrioadenite bilateral causada pelo vírus Epstein-Barr: relato de caso.

UNLABELLED: The authors present a rare case of acute bilateral dacryoadenitis in association with infectious mononucleosis. A 27 year-old woman had acute bilateral lacrimal gland enlargement with inflammatory signs. The CT scan findings and laboratorial investigations confirmed the diagnosis of infectious mononucleosis. The systemic treatment with intravenous steroids was initiated leading to complete remission of the signs and symptoms. COMMENTS: Dacryoadenitis is an uncommon manifestation of infectious mononucleosis and may minimize other signs of the disease. Mononucleosis has to be considered in acute dacryoadenitis cases. Systemic steroids contribute to the fast regression of inflammatory condition.

Severe focal sialadenitis and dacryoadenitis in NZM2328 mice induced by MCMV: a novel model for human Sjögren's syndrome.

The genetic and environmental factors that control the development of Sjögren's syndrome, an autoimmune disease mainly involving the salivary and lacrimal glands, are poorly understood. Viruses which infect the glands may act as a trigger for disease. The ability of sialotropic murine CMV (MCMV) to induce acute and chronic glandular disease was characterized in an autoimmune-prone mouse strain, NZM2328. MCMV levels were detectable in the salivary and lacrimal glands 14-28 days after i.p. infection and correlated with acute inflammation in the submandibular gland. After latency, virus was undetectable in the glands by PCR. At this stage, NZM2328 female mice developed severe chronic periductal inflammation in both submandibular and lacrimal glands in contrast to the much milder infiltrates found in female B6-lpr and male NZM2328. The focal infiltrates consisted of CD4+ and B220+ cells as opposed to diffuse CD4+, CD8+, and B220+ cells during acute infection. Salivary gland functional studies revealed a gender-specific progressive loss of secretory function between days 90 and 125 postinfection. Latent MCMV infection did not significantly affect the low incidence of autoantibodies to Ro/SSA and La/SSB Ags in NZM2328 mice. However, reactivities to other salivary and lacrimal gland proteins were readily detected. MCMV infection did not significantly alter the spontaneous onset of kidney disease in NZM2328. Thus, chronic inflammation induced by MCMV with decreased secretory function in NZM2328 mice resembles the disease manifestations of human Sjögren's syndrome.

Encephalomyocarditis (EMC) virus-induced sialodacryoadenitis in mice.

The mode of occurrence of the D variant of encephalomyocarditis (EMC-D) virus-induced acute sialodacryoadenitis was investigated using three strains of mice differing in their sensitivity to EMC-D virus-induced diabetes (C57BL/6: resistant; BALB/c: moderately sensitive; DBA/2: highly sensitive). Mice were intranasally inoculated with high (10(5) PFU/mouse) or low dose (10(2) PFU/mouse) of EMC-D virus. Although there were individual differences, the blood virus titer generally reached the peak earlier in the high-dose group than in the low-dose group. Signals of viral RNA and histopathological changes were seen in parotid glands and intraorbital and extraorbital lachrymal glands. In these glands, signals of viral RNA and histopathological changes were detected only in acinar cells and initial lesions were characterized by pyknosis of acinar cells. Coagulative necrosis with interstitial inflammatory cell infiltration developed later in parotid glands of BALB/c mice of the high-dose group and in intraorbital and extraorbital lachrymal glands of all groups except for C57BL/6 mice of the low-dose group. Such changes were not observed in epithelial cells of the ductal system. The present results indicate that EMC-D virus shows clear tissue and cell tropism within the salivary and lachrymal glands, probably due to the distribution of receptors for EMC virus.

Epstein-Barr virus dacryoadenitis resulting in keratoconjunctivitis sicca in a child.

PURPOSE: To describe a case of severe dry eye syndrome in a child. METHODS: Observational case report. The authors describe a 10-year-old male with severe dry eyes who was profoundly disabled by pain and photophobia despite aggressive conventional therapy. Lacrimal gland histology was consistent with the primary Sjögren syndrome, and serologic and immunohistologic evidence supported the hypothesis of Epstein-Barr virus causality. RESULTS: Treatment with systemic acyclovir and cyclosporin A resulted in dramatic and rapid reversal of the profound sicca syndrome and enabled the patient to resume his normal activities. CONCLUSION: Epstein-Barr virus dacryoadenitis should be considered in the differential diagnosis of keratoconjunctivitis sicca in children. Epstein-Barr virus can cause keratoconjunctivitis sicca, which can be treated successfully with acyclovir therapy in addition to suppression of the inflammatory response.

Epstein-Barr virus dacryoadenitis.

PURPOSE: To describe the clinical features of lacrimal gland inflammation associated with Epstein-Barr virus infection. METHODS: The clinical records, laboratory data, and radiographs of patients who had inflammation of one or both lacrimal glands that had begun less than 4 weeks previously were reviewed. RESULTS: Sixteen patients with dacryoadenitis were encountered between 1980 and 1996, a cumulative frequency of approximately one case per 10,000 new ophthalmic outpatients. Six individuals had serologic or other evidence of recent Epstein-Barr virus infection and were distinguished by the presence of regional lymphadenopathy, no purulent discharge, and a duration of symptoms of 6 weeks. CONCLUSION: Epstein-Barr virus is a probable cause of unilateral and bilateral dacryoadenitis in young adults.

Infectious mononucleosis presenting with dacryoadenitis.

BACKGROUND: A case of severe, bilateral, acute dacryoadenitis in a rarely reported association with infectious mononucleosis is described. METHODS: A 16-year-old girl had acute, bilateral, lacrimal gland enlargement demonstrated with computed tomographic scanning of the orbits. Clinical findings and laboratory investigations confirmed the diagnosis of infectious mononucleosis. Treatment with systemic steroids was initiated. RESULTS: There was rapid resolution of the clinical findings with systemic steroids. CONCLUSION: Dacryoadenitis is an uncommon presentation of infectious mononucleosis and may overshadow the other manifestations of this disease. The diagnosis of infectious mononucleosis should be considered in patients with acute dacryoadenitis. Systemic steroids play an important role in rapidly resolving the dacryoadenitis.

Chronic dacryosialadenitis in HTLV I associated myelopathy.

A prospective study was carried out on 48 patients with HTLV I associated myelopathy/tropical spastic paraparesis (HAM/TSP) to assess the association between this entity and Sjögren's syndrome. Fourteen patients (29.1%) had chronic dacryosialadenitis confirmed by a positive Schirmer's test and salivary gland biopsy. None of these patients had evidence of collagen disease and tests for Ro, La, and rheumatoid factor were negative except in one case. Therefore, the dacryosialadenitis could not be classified as either primary or secondary Sjögren's syndrome. Ten of the 14 patients (71.4%) had other systems (haematological, articular, dermatological, or respiratory) involved apart from the neurological and exocrine gland pathology. The findings suggest that the dacryosialadenitis associated with HTLV I is a disease of viral origin distinct from Sjögren's syndrome.