Diagnosis and treatment of chlamydial conjunctivitis

  A, the characteristics of Chlamydia Chlamydia is a microorganism between bacteria and viruses, classified in the Richter class, Chlamydia order. With cell walls and cell membranes, bipartite reproduction, can be parasitic in the cell to form inclusion bodies. Chlamydia is divided into two genera. Genus I is Chlamydia trachomatis, which can cause trachoma, inclusion body conjunctivitis and lymphogranuloma; Genus II is Chlamydia psittaci, which can cause psittacosis. Chlamydial conjunctivitis including trachoma, inclusion body conjunctivitis, venereal lymphogranulomatous conjunctivitis, etc.
  Second, trachoma
  Trachoma (trochoma) is a chronic infectious conjunctival keratitis caused by Chlamydia trachomatis (chlamydia) infection, and is one of the major diseases causing blindness. Trachoma is a chronic infectious conjunctival keratitis caused by Chlamydia, one of the major diseases that cause blindness. 300 to 600 million people worldwide are infected with trachoma, and the rate and severity of infection are closely related to local living conditions and personal hygiene habits. before the 1950s, the disease was widely prevalent in China, and was the primary cause of blindness at that time. after the 1970s, with the improvement of living standards, general health awareness and medical conditions, its incidence has greatly decreased, but it is still one of the common conjunctival diseases.
  Etiology] Chlamydia trachomatis was first isolated in the world in 1955 by Tang Feifan and Zhang Xiaolou using chicken embryo culture method. Antigenicity can be divided into 12 immunotypes, such as A, B, Ba, C, D, E, F, J, H, I, K. Endemic trachoma is mostly caused by A, B, C or Ba antigen type, D to K type mainly causes genitourinary system infection and inclusion body conjunctivitis. Zhang Li and Zhang Xiaolou et al. (1990) examined the immunotypes of Chlamydia trachomatis in northern China and showed that trachoma in northern China is predominantly type B, followed by type C. Epidemiological information on the incidence in other regions of China is lacking. Trachoma is bilaterally transmitted through direct contact or indirect transmission of contaminants, and arthropod insects are also vectors of transmission. Susceptibility risk factors include poor sanitation, poor nutrition, and hot or dusty climates. It is easily spread in tropical and subtropical regions or during the dry season.
  Clinical presentation】 Acute trachoma infection occurs mainly in preschool and early school-age children, but early scarring complications begin to become apparent around age 20. Severe eyelid and corneal comorbidities can occur at all times in adulthood. The incidence and severity of acute trachoma are comparable in men and women, but severe scarring is two to three times higher in women than in men, and it is hypothesized that this difference is related to close contact between the mother and the acutely infected child.
  The onset of disease is generally slow, mostly in both eyes, but can vary in severity. The incubation period after Chlamydia trachomatis infection is 5 to 14 days. In young children with trachoma, the symptoms are insidious and can resolve on their own without sequelae. In adults, trachoma has a subacute or acute course with early complications. Trachoma initially manifests as follicular chronic conjunctivitis and later progresses to conjunctival scar formation.
  Symptoms in the acute phase include photophobia, lacrimation, foreign body sensation, and more mucus or mucopurulent discharge. The eyelids may be red and swollen, the conjunctiva may be markedly congested, the papillae may be enlarged, and the upper and lower fornix may be filled with follicles.
  In the chronic phase, there is no obvious discomfort, only itching, foreign body sensation, dryness and burning sensation in the eyes. Conjunctival congestion decreases and the conjunctiva becomes smudged and hypertrophied, with papillae and follicular hyperplasia. The lesion is prominent in the superior fornix and superior lid margin of the conjunctiva, and a drape-like corneal vascular opacity may appear. During the course of the lesion, the conjunctival lesion is gradually replaced by connective tissue, forming a scar. The earliest of these is in the inferior lid sulcus of the upper lid conjunctiva, called the Arlt line, which gradually becomes reticulated and later all becomes a white smooth scar. Scarring of the corneal limbal follicles is known clinically as Herbet’s notch. Trachomatous corneal vascular opacification and lid conjunctival scarring are characteristic signs of trachoma.
  The irritation may be more severe with repeated infections and bacterial infections, and visual loss may occur. Complications such as lid entropion and impingement, ptosis, lid bulb adhesions, corneal clouding, substantial conjunctival dryness, and chronic dacryocystitis occur in the late stages. The symptoms are more pronounced and can severely affect vision and even blindness.
  To standardize epidemiological investigations and guide treatment, the phenotypes of trachoma have been staged internationally. The MacCallan staging method is commonly used
   Stage I: Early trachoma. Immature follicles appear in the upper lid conjunctiva, with mild subepithelial corneal clouding, diffuse punctate keratitis and fine corneal vascular opacities above.
   Stage II: active trachoma.
   Stage IIa: Follicular hyperplasia. Corneal opacification, subepithelial infiltration and marked superficial corneal vascular opacification above.
   Stage IIb: papillomatous hyperplasia. Follicular blurring. Follicular necrosis, superficial corneal vascular opacification above and subepithelial infiltration can be seen. Scarring is not evident.
  Stage III: scar formation. Same as our stage II.
   Stage IV: Inactive trachoma. Same as our stage III.
  In 1979, we also developed a staging method suitable for our national conditions. Namely.
  Stage I (progressive active stage) upper lid conjunctival papillae and follicles coexist, with blurred upper vault conjunctiva and corneal vascular opacification.
  Stage II (regressive stage) the upper lid conjunctiva begins to appear from scarring until most of it becomes scarred. Only a few active lesions remain.
  In stage III (complete scar stage) the active lesions of the upper lid conjunctiva disappear completely and are replaced by a scar, which is not infectious.
  In 1987, the World Health Organization (WHO) introduced a new simple staging method to evaluate the severity of trachoma. The criteria were as follows.
  Follicular conjunctival inflammation (FCLI): 5 or more follicles in the upper lid conjunctiva.
  Diffuse conjunctival inflammation: diffuse infiltration, papillary hyperplasia, and vascular blurred areas >50%.
  tarsal conjunctival scarring: typical lid conjunctival scarring.
  Trichiasis: severe impingement or entropion of the eyelid.
  Corneal opacification: varying degrees of corneal opacification.
  Conjunctival follicles and diffuse conjunctival infections are active trachoma and should be treated; conjunctival scarring is the basis for previous trachoma; impingement is potentially blinding and requires corrective eyelid surgery; and corneal opacification is end-stage trachoma.
  Most trachoma can be diagnosed based on specific signs such as papillae, follicles, epithelial keratitis, vascular opacities, corneal limbal follicles, and Herbert’s sulcus. The WHO requires that at least two of the following criteria be met for the diagnosis of trachoma.
  Five or more follicles in the upper lid conjunctiva.
  Typical lid conjunctival scarring.
  Corneal rim follicles or Herbet’s hollows.
  Extensive corneal vascular opacification.
  In addition to the clinical presentation, laboratory tests can establish the diagnosis. Trachoma cytology is typically characterized by the detection of lymphocytes, plasma cells and polymorphonuclear leukocytes, but the cytology has a high rate of false positives.
  Giemsa staining after conjunctival scraping may reveal inclusion bodies located in the perinuclear or red cytoplasm. Modified Diff-Quik staining reduces the time to detect inclusion bodies to a few minutes. Fluorescently labeled monoclonal antibody kits for detection of cell-scraping Chlamydia antigens, enzyme-linked immunoassays, and polymerase chain reaction are highly sensitive and highly specific, but require a more skilled operator and are expensive. Chlamydia trachomatis culture requires radiation irradiation or cell stabilizer (such as actinomycin) pretreatment, usually after 48-72 hours of growth with iodine staining monolayer cells, or by special anti-chlamydial monoclonal antibody detection, is an important laboratory test, but the technical requirements are high, can not be widely used.
  Differential diagnosis】It needs to be differentiated from other follicular conjunctivitis.
  Chronic follicular conjunctivitis (chronic follicular conjunctivitis): The cause is unknown. It is common in children and adolescents, both bilaterally. Uniformly sized, well-arranged follicles are seen in the lower dome and lower lid conjunctiva, with no tendency to fuse. The conjunctiva is congested with discharge but is not hypertrophic and heals spontaneously after several years without traces of corneal opacification. Those without inflammatory symptoms such as discharge and conjunctival congestion are called conjunctival folliculopathy. It usually does not require treatment and is only treated as chronic conjunctivitis when there are self-conscious symptoms.
  Spring conjunctivitis: This disease has large, flattened papillae of lid conjunctival hyperplasia, no lesions in the upper dome, and no corneal vascular opacities. A large number of eosinophils are seen in the smear of conjunctival secretions.
  Inclusion body conjunctivitis: The main difference between this disease and trachoma is the prominent subfollicular dome and lower lid conjunctiva without corneal vascular opacification. It can be differentiated from it in the laboratory by immunofluorescence testing with monoclonal antibodies against different chlamydial antigens to identify their antigenic serotypes.
  Giant papillary conjunctivitis: The conjunctival papillae caused by this disease can be confused with trachomatous follicles, but there is a clear history of corneal contact lens wear.
  Treatment】Including systemic and topical ocular medication and treatment of complications.
  Topical eye drops such as 0.1% rifampicin eye drops, 0.1% phthalbutamide eye drops or 0.5% neomycin eye drops are used 4 times/d. Erythromycin and tetracycline eye ointments are used at night for a minimum of 10-12 weeks. After a period of treatment, follicles may still be present in the upper lid conjunctiva, but this is not a basis for treatment failure.
  Acute or severe trachoma should be treated with systemic antibiotics for a general course of 3 to 4 weeks. Doxycycline 100 mg can be given orally 2 times/d; or erythromycin 1 g/d in four oral doses. Surgical correction of impingement and entropion is the key measure to prevent late trachoma scar formation leading to blindness.
  Prevention and prognosis】 Trachoma is a long-lasting chronic disease, and 6 to 9 million people have been blinded by trachoma. With appropriate treatment and improved hygiene, trachoma can be alleviated or symptoms can be reduced to avoid serious complications. In endemic areas, reinfection is common and requires repeat treatment. Preventive measures and repeat treatment should be combined. Good hygienic habits should be cultivated to avoid contact transmission, improve the environment, and strengthen the hygienic management of the service industry.
  Inclusion body conjunctivitis
  Inclusion conjunctivitis (inclusion conjunctivitis) is an acute or subacute follicular conjunctivitis caused by Chlamydia trachomatis type D to K that is transmitted through sexual contact or the birth canal. Inclusion conjunctivitis occurs in young people who are sexually active, mostly bilaterally. Chlamydia infects the male urethra and female cervix and spreads to the conjunctiva through sexual contact or hand-eye contact, and swimming pools can indirectly transmit the disease. Newborns delivered through the birth canal may also be infected. Due to the different manifestations, it is clinically divided into neonatal and adult inclusion body conjunctivitis.
  Clinical manifestations
  (A) Adult inclusion body conjunctivitis
  The disease develops in one or both eyes 1 to 2 weeks after exposure to the pathogen. The manifestation is mild to moderate eye redness, eye irritation and mucopurulent discharge, some patients may be asymptomatic. The eyelids are swollen, with significant conjunctival congestion and conjunctival follicle formation in the lid conjunctiva and dome, with varying degrees of papillary reaction, mostly located inferiorly. The preauricular lymph nodes are enlarged, and the acute inflammation gradually decreases after 3 to 4 months, but the conjunctival hypertrophy and follicles persist for 3 to 6 months before returning to normal. Sometimes a peripheral corneal epithelial or subepithelial infiltrate, or a small superficial vascular opacity (<1-2 mm), without an anterior chamber inflammatory response, is seen. The timing and extent of conjunctivitis in volunteers inoculated with adult inclusion body chlamydia serotype were dose-dependent, and otitis media occurred in 14% of volunteers, whereas iritis was very rare, suggesting that Chlamydia trachomatis readily spreads infection through tears from the nasolacrimal duct to the nasal mucosa, but has difficulty crossing the cornea into the uvea. Clinically, adult inclusion body conjunctivitis may have conjunctival scarring but no corneal scarring, and rarely causes iridocyclitis. Signs of chlamydial infection in other sites such as the genitals and pharynx may also be present.
  (ii) Neonatal inclusion body conjunctivitis
  The incubation period is 5 to 14 days after birth, with signs appearing on the first day after birth in cases of premature rupture of membranes. The infection is mostly bilateral, and the newborn starts with aqueous or a little mucus-like discharge, which increases significantly and becomes purulent as the disease progresses. Conjunctivitis persists for 2 to 3 months before the appearance of milky white glossy follicles, which are larger than those of viral conjunctivitis. Severe cases have pseudomembrane formation and conjunctival scarring. Most neonatal chlamydial conjunctivitis is mildly self-limiting, but corneal scarring and neovascularization may be present. Chlamydia can also cause life-threatening infections elsewhere in the neonate, such as chlamydial otitis media, respiratory tract infections, and pneumonia. Chlamydia trachomatis can co-infect with herpes simplex virus. In addition to systemic infection, the possibility of ocular co-infection should be noted during the examination.
  Diagnosis】Diagnosis is not difficult based on clinical manifestations. Laboratory tests are the same as for trachoma. Basophilic inclusion bodies are readily detected in the cytoplasm of epithelial cells in neonatal inclusion body conjunctivitis. Serologic testing is of little value in the diagnosis of ocular infection, but testing for IgM antibody levels can be of great help in the diagnosis of chlamydial pneumonia in infants and children. Neonatal inclusion body conjunctivitis needs to be differentiated from infections caused by Chlamydia trachomatis and gonococcus.
  Treatment】Chlamydial infection can spread to the respiratory and gastrointestinal tracts, so oral medication is necessary. Infants and children can be given erythromycin (40mg/kg?d) orally in four doses for at least 14 days. If there is a relapse, the entire dose needs to be given again. Adults are treated with oral doxycycline (100mg twice/d) or erythromycin (1g/d) for 3 weeks. Topical antibiotic eye drops and eye ointment such as 15% sodium sulfadoxine acetate, 0.1% rifampin, etc.
  Prognosis and prevention】 Untreated inclusion body conjunctivitis lasts from 3 to 9 months, with an average of 5 months. The duration of the disease is shortened after treatment with standard protocols, and the recurrence rate is low.
  Education of young people about hygiene, especially sexuality, should be enhanced. High-quality prenatal care including detection and treatment of genital tract chlamydia infection is essential for successful prevention of neonatal infection. Effective prophylactic medications include 1% silver nitrate, 0.5% erythromycin, and 2.5% povidone iodine. Of these, 2.5% povidone iodine is the most effective and least toxic for eye spotting.