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REVIEW ARTICLE
Year : 2022 | Volume
: 29
| Issue : 1 | Page : 51-55
Tubercular episcleritis: A review of literature
Tariq M Aldebasi1, Abdulelah A Alasiri2, Muhannad A Alnahdi3, Abdulrahman Alfarhan4
1 Department of Ophthalmology, King Abdulaziz Medical City, National Guard-Health Affairs; Department of Ophthalmology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Ophthalmology, King Abdulaziz Medical City, National Guard-Health Affairs, Riyadh, Saudi Arabia
3 Department of Ophthalmology, King Abdulaziz Medical City, National Guard-Health Affairs; Department of Ophthalmology, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
4 Department of Training and Scholarship, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
Correspondence Address:
Dr. Muhannad A Alnahdi
College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia, P. O. Box: 3660, Riyadh 11481
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/meajo.meajo_315_21
Abstract
Episcleritis is rarely reported to be associated with tuberculosis (TB). In this review, we highlight this underreported entity and elaborate on the natural history of the reported cases in the literature. Eighteen articles were found to describe numerous cases throughout the past century. Forty patients diagnosed with tuberculous episcleritis were found in the literature. The majority of the patients presented with a latent form of TB and fewer cases were linked with active/pulmonary disease. The natural history of episcleritis was found to have chronic and recurrent attacks refractory to traditional treatment, and the most commonly reported type was the nodular form. The described cases were eventually treated by quadruple antituberculous therapy, and fortunately, recurrence after treatment completion was not documented. It is imperative to highlight such entities that may be underreported in endemic countries, as successful therapy would decrease ocular morbidity and prevent potential unforeseen tuberculous complications.
Keywords: Episcleritis, nodular, simple, tubercular, tuberculosis
Introduction 
Tuberculosis (TB) is an airborne infectious disease that primarily affects the lungs. It is the leading cause of morbidity and mortality worldwide from a single infectious agent. The number of TB infections has increased significantly in the world in association with higher rates of multidrug-resistant TB, human immunodeficiency virus epidemic, and international migration.[1],[2] The World Health Organization reported that one-third of the world's population are infected with TB, only 10% of which have active symptoms and 90% have latent TB.[3] Individuals with latent TB are noncontagious, yet at any time during their life, TB may become reactivated, and they can develop active clinical symptoms.
TB does not always settle in the respiratory system. It has multiple extrapulmonary manifestations, of them, the eyes. Ocular TB (OTB) is a rare extrapulmonary form of the disease, not to be underestimated, considering its potential impact on visual loss in patients diagnosed with the disease. In endemic regions, it is estimated that the prevalence of OTB in individuals infected with TB ranges from 10% to 26%.[4]
OTB is discussed in depth many review articles. Those articles elaborated on the different manifestations of TB, but very few mentioned episcleritis. Even upon discussing episcleritis, these reviews did not thoroughly cover the entity.[5],[6],[7],[8] Furthermore, remote review article about episcleritis carried a similar lack of knowledge about the characteristics of tuberculous episcleritis.[8] Thus, we find that the available review articles in the literature have fallen short to provide robust data about tuberculous episcleritis and is still lacking details on the clinical spectrum of Mycobacterium tuberculosis (MTB) effect on the episclera. This review will focus on the episcleral form of TB.
Search Strategy A comprehensive search of the literature was performed using PubMed and Google Scholar engines. The search strategy was done using Medical Subject Headings terms, keywords, truncation, and wildcard symbols. The following keywords were used by utilizing Boolean operators: (a) tuberculosis OR tuberculous OR MTB OR tubercul* OR TB; (b) episcleritis OR episclera OR episcleral, and (c) a AND b. The search was not limited by the time of publication or the written language. Two authors retrieved all studies that contained the search terms and reviewed the abstracts to check for relevance. References of the retrieved articles were also reviewed to identify any other articles of interest that may not have been identified by the search terms.
Study Characteristics The search yielded 18 articles. The identified designs of the articles were case reports and retrospective chart reviews published between 1923 and 2020. A thorough manuscript review was performed by two authors to extract the required data which included basic demographics, presenting symptoms, type of TB, laboratory results, slit-lamp findings, and medical treatment. These studies included 40 eyes diagnosed with tubercular episcleritis. Noteworthy, not all articles have fully reported the relevant data of the cases. The characteristics of all studies extracted for inclusion are shown in [Table 1].
Table 1: Descriptive characteristics of the diagnosed tubercular episcleritis cases in the literatureEpidemiology: Basic Demographic
Eight studies detailed the gender of the patients, and the approximate male to female ration is 1:4, two males and nine females.[9],[10],[12],[14],[15],[17],[19],[20],[21],[23] Age ranged from 6 to 57 years old with patients' mean age of 32 years. The origin of the published studies was noticed in endemic areas such as India, Nepal, and Sri Lanka.[12],[15],[16],[17],[18],[20],[22],[24],[25],[26] Furthermore, several reports originated from the USA, UK, and European countries.[9],[10],[11],[13],[14],[17],[21],[23] Two studies were published before the discovery of streptomycin and its activity against MTB in 1944.[9],[10],[27]
Patient's Presentation Of the symptoms reported, all cases presented with redness and pain/tenderness. Impaired vision was reported in five patients. Two patients had concurrent scleritis upon their diagnosis; otherwise, there were no other reported ocular manifestations. The dominance of tubercular episcleritis was found to be unilateral among reported cases (n = 12). Nodular episcleritis was seen in 10 (25%) of the reported cases [Figure 1], two cases (4.8%) were reported as simple episcleritis, and the rest were unspecified. Latent TB was found in 17 of the reported cases, while 13 cases had active/pulmonary TB, and the rest had confirmed diagnosis but unspecified. Furthermore, one case had a hematogenous spread of granulomatous dermatitis and lobular panniculitis.
Figure 1: Nodular episcleritis of the right eye with superficial vasodilatation. Permitted reproduction from Belakbir, T. [29] Copyright © 2020 Elsevier Masson SAS. All rights reserved Diagnosis The diagnosis of OTB is quite challenging. The literature in this area is centered around that most cases have a presumptive diagnosis determined by clinical suspicion, laboratory evidence of TB, and positive response to antituberculous therapy (ATT).[28] OTB cannot be easily excluded, as extrapulmonary TB is diagnosed in 60% of patients without any evident pulmonary TB.[29]
Diagnosis of episcleritis is generally straightforward, as most cases are idiopathic and spontaneously resolved within 2–3 weeks.[30],[31] However, when episcleritis becomes indolent and chronic, it can be associated with infectious etiologies or systemic autoimmune diseases, and, in such cases, a systematic review of symptoms and complete physical examination should be done. Afterward, appropriate laboratory tests are usually required. A detailed discussion of the episcleritis diagnostic approach is not within the scope of this review. Our discussion will be limited to tuberculous episcleritis to highlight such ocular/systemic pathology that might be overlooked by ophthalmologists.
History Tuberculous episcleritis is often suspected among the referenced cases in this review, as patients have a positive history of residence or relocation from endemic countries, had a history of contact with confirmed pulmonary TB, or have concurrent active pulmonary disease. Furthermore, tuberculous episcleritis was reported as recurrent in few cases, while most cases were subjected to further testing and investigation due to the prolonged or refractory nature to the traditional treatment.[11],[12],[15],[16],[22],[25] Based on these elements, TB might be suspected, and further investigations are ordered. We found that reported cases with such elements of history may have aided and clued the ophthalmologists about the diagnosis.
Investigations Purified protein derivative (PPD) is considered a screening test for patients with suspected tuberculous exposure. The sensitivity and specificity of the test are not optimal, as previous review articles have conveyed, thus its utility depends on the clinical context and high index of suspicion.[28],[32],[33] In TB episcleritis, not all reports in the literature described the results of this test; all reported PPD tests were found to be positive.[12],[14],[15],[17],[19] The reports described very high induration clueing into the etiology of their patient's underlying pathology.
Interferon Gamma Release Assay is also used as a screening test for patients with suspected TB. The test introduces MTB antigens and measures the released interferon-gamma from T-cells. True usability in OTB is still a matter of research, and earlier studies have not confirmed its superiority over PPD in TB-related uveitis.[34],[35],[36] The test was reported in one case diagnosed with episcleritis and was found to have a positive result.[21] The economic status of the countries may have led to this utilization discrepancy between the two tests, along with the feasibility of utilizing the former.
Polymerase chain reaction (PCR) is an excellent diagnostic tool that carries high sensitivity and specificity. The swensitivity of the test highly depends on the presence of targeted proteins (IS6110 MPB64, and protein b), thus, the absence of such proteins in the captured sample may raise the likelihood of false-negative results.[37] Furthermore, utilization of this diagnostic modality may be hindered by low concentration of the organism within a sample and low volume sample of ocular fluids. Another predicament is the possibility that the occurring inflammation is due to hypersensitivity to mycobacterium antigens and not the actual organism. Furthermore, high cost and technical difficulties make PCR less feasible for institutions in countries with high TB endemicity. PCR was utilized in three patients, but only one case became positive.[15],[17],[21] The positive case was found to have pulmonary TB; however, the other two cases had latent TB with a negative chest X-ray.
The gold standard test for the diagnosis by the capture of the mycobacterium organism from an ocular specimen either fluid or tissue biopsy for histopathology and culture. An ocular biopsy is rarely attempted due to impracticability and adverse complications. In fact, these may be nondiagnostic as sample results are negative due to the low concentration of the organism.[32] Ocular biopsy was not attempted in any case in this review. In general, culture may be used to ascertain the diagnosis but may not necessarily change the treatment plan if found negative due to similar limitations with preceding diagnostic modalities along with the extended time required. Culturing of the conjunctival swab was attempted in few cases and was only turned to be positive in one case diagnosed with pulmonary TB, while the other cases were labeled as latent TB.[12],[14],[19]
Treatment ATT is the mainstay of treatment for OTB. Of the reports that discussed the treatment, nearly all episcleritis cases were treated by quadruple ATT. However, cases published before the first description of the ATT utilized other treatment modalities. Symptomatic improvement was noted as early as 2 months after initiation of treatment, and only one case was diagnosed while being on anti-TB therapy.[25]
Centers for Disease Control and Prevention recommendation states that short-course (3–4 months) rifamycin-based (rifampin, rifabutin, and rifapentine) treatment regimens are preferred over the longer-course (6–9 months) isoniazid monotherapy for the treatment of of latent tuberculosis infection for patients with good drug tolerability and the absence of inter-drug interactions.[38] Treatment regimens that are strongly recommended for latent TB are (1) isoniazid and rifapentine (once weekly for 3 months) or (2) rifampin (daily for 4 months).[38] Proactive surveillance for possible side effects is vital. Common side effects include hepatitis, skin reactions, gastrointestinal intolerance, hematological reactions, and renal failure.[39] TB multichemotherapy carries an increased risk for adverse effects that may limit its effectiveness by premature discontinuation; however, none of the reports have described any adverse effect of the regimen, and all patients tolerated the therapy quite well with resolution of their complaints. Follow-up surveillance after treatment completion did not reveal any flares or any recurrences of any episode.
Challenges Episcleritis is usually taken as self-resolving owing to its idiopathic etiology in most instances. Although merely based on observational reports, the available literature may consolidate the association between TB and episcleritis, adding a challenging feature to this entity. Clinicians may label such presentations as presumed cases due to the lack of practical definitive diagnostic modalities and rely on patients' subjective improvement after initiating ATT. The ability to detect potential cases may be hurdled by the inaccessibility to specialists who can help manage and shed light on the implications of this underreported entity. The investigational efforts to discover TB may pose further financial constraints on health-care systems, especially in underdeveloped endemic countries. Another challenging pitfall is the balancing between offering the traditional treatment or further testing and treatment. This article aids in promoting the knowledge of this potential association across ophthalmologists and other clinicians. Clinical suspicion is the best tool at hand to efficiently stratify patients to avoid over screening and treatment and accurately deliver the needed care.
Conclusion In the light of the scarce literature on this entity, this review highlights TB to be an important cause of episcleritis that may be overlooked. In certain cases, episcleritis was the only manifestation in patients with the latent form of TB. This should be emphasized among clinicians who practice in areas with high endemicity, as such findings led toward treating patients and alleviating their ocular complaints and potential systemic morbidity. Even though the literature showed the absence of complications, benefits, and adversities of such treatment must be clearly communicated to the patients. Catching such a diagnosis would prevent the catastrophic sequelae of untreated TB as patients in latency can transform to active or miliary TB once their immunity is compromised. It is imperative to highlight this entity and alert ophthalmologists to have a high index of suspicion upon facing patients with such complaints.
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Conflicts of interest
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References 
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