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Year : 2021  |  Volume : 3  |  Issue : 1  |  Page : 40

Eyelid edema – An unusual presentation of ocular tuberculosis

1 Department of Ophthalmology, Hospital Prof. Doutor Fernando Fonseca E.P.E., Amadora, Lisbon, Portugal
2 Department of Anatomic Pathology, Hospital Prof. Doutor Fernando Fonseca E.P.E., Amadora, Lisbon, Portugal

Date of Submission17-Oct-2021
Date of Acceptance08-Nov-2021
Date of Web Publication09-Dec-2021

Correspondence Address:
Dr. Joana Roque
Department of Ophthalmology, Hospital Prof. Doutor Fernando Fonseca, IC19, 2720- 276 Amadora, Lisbon
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_114_21

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We describe the case of a 71-year-old woman with periocular tuberculosis manifesting as eyelid edema. The diagnosis of tuberculosis infection was particularly difficult given the atypical presentation, the negative result of interferon-gamma release assay, and the absence of active or past pulmonary disease. Skin biopsy and its analysis with polymerase chain reaction (PCR) enabled the definitive diagnosis of Mycobacterium tuberculosis infection. This represents an exceptionally rare form of eyelid tuberculosis and highlights the importance of a thorough investigation in the diagnostic workup of unspecified and refractory cases of eyelid edema that should include histopathological tissue analysis.

Keywords: Eyelid diseases/diagnosis, ocular tuberculosis/diagnosis, ocular tuberculosis/pathology

How to cite this article:
Roque J, Coutinho I, Alves A, Ferreira M. Eyelid edema – An unusual presentation of ocular tuberculosis. Pan Am J Ophthalmol 2021;3:40

How to cite this URL:
Roque J, Coutinho I, Alves A, Ferreira M. Eyelid edema – An unusual presentation of ocular tuberculosis. Pan Am J Ophthalmol [serial online] 2021 [cited 2022 Dec 3];3:40. Available from: https://www.thepajo.org/text.asp?2021/3/1/40/332114

  Introduction Top

Periorbital edema can represent a diagnostic challenge. The differential diagnoses are countless and comprise both inflammatory (infectious/noninfectious) and noninflammatory diseases. Eyelid infection by Mycobacterium tuberculosis is an exceptionally rare cause of periorbital edema.[1] We report a case of periorbital tuberculosis presenting as diffuse unilateral periorbital edema.

  Case Report Top

A 71-year-old Indian woman residing in Portugal for several decades presented to the department of ophthalmology with complaints of progressive swelling of the left periorbital region over the course of 2 months. The patient had no past history of tuberculosis or any other significant systemic diseases. She denied other ocular or systemic symptoms. Physical examination showed a painless and mildly erythematous diffuse edema of the left periorbital region, with no masses or nodules on palpation [Figure 1]. Further ocular examination was unremarkable. No regional lymphadenopathy could be detected.
Figure 1: Photograph showing the diffuse left periorbital edema

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The patient was managed with an empirical regimen that primarily included topical steroids and oral antibiotics, subsequently oral antihistamines, and finally, a short course of systemic corticosteroids. Due to lack of improvement with empiric treatment, a further study was conducted. Magnetic Resonance Imaging (MRI) scans of the orbits were obtained to further define the extent and nature of the swelling. These confirmed thickening and edematous changes of the left periorbital tissues, with no other lesions nor extension to the post septal orbital space [Figure 2].
Figure 2: (H and E; a: low power; b: high power) Histopathological skin biopsy showing nonnecrotizing granulomatous inflammation (▸) in perivascular regions of the deep dermis

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Blood tests were inconclusive. These included the following assays: complete blood count, kidney and liver function tests, serum protein electrophoresis, C-reactive protein, erythrocyte sedimentation rate, angiotensin-converting enzyme, lysozyme, human immunodeficiency virus and hepatitis B and C screening, Trichinella spiralis serology, and also the QuantiFERON-TB Gold interferon-gamma release assay (IGRA).

An incisional biopsy of the superior eyelid skin was performed, revealing a nonnecrotizing granulomatous inflammation in perivascular and perineural regions of the deep dermis, with no evidence of vasculitis [Figure 2]. Histochemical stains (Ziehl–Neelsen, Grocott, and periodic acid–Schiff) showed no evidence of acid-fast bacteria or fungi. High-resolution chest computed tomography was performed, showing no evidence of pulmonary tuberculosis or sarcoidosis. Due to suspicion of a local mycobacterial infection, real-time polymerase chain reaction (PCR) for mycobacteria was performed in the paraffin-embedded tissue, confirming the presence of M. tuberculosis DNA.

The patient was therefore diagnosed with periorbital tuberculosis, and quadruple antituberculous medication (isoniazid, rifampin, pyrazinamide, and ethambutol) was prescribed. However, owing to adverse effects on the oral cavity, she did not follow this regimen, and decided to permanently abandon the treatment. At 1-year follow-up, the clinical condition remains stable.

  Discussion Top

The workup of periorbital edema can present a challenge to many physicians. Swelling of the periorbital tissues may be associated with numerous and miscellaneous conditions: infectious, noninfectious (inflammatory/neoplastic), drug-induced, and postsurgery/trauma. Infectious causes, arising from systemic or local infections around the eye, are among the first to rule out. These include common agents such as Staphylococcus aureus and Streptococcus pneumoniae but also numerous unusual microorganisms: parasites, such as Trichinella species; viral infections, such as hepatitis B; and spirochetal infections.

M. tuberculosis is an important suspect in cases of atypical cellulitis and chronic or unusual eyelid conditions.[1] Tuberculosis is a multisystem granulomatous disease that primarily affects the lungs but can involve practically every organ, including the eye and periocular tissues (ocular tuberculosis). Most ocular tuberculosis cases are secondary, usually resulting from the hematogenous spread from a distant primary focus of past tuberculosis that might not be evident clinically or radiographically.[2] The clinical manifestations of ocular tuberculosis are nonspecific and protean,[2] with anterior uveitis and choroiditis being the most common presentations.[1]

Isolated eyelid tuberculosis is an exceptionally rare presentation of tuberculosis.[1],[3] Most authors report nodular lesions that may simulate chalazia. Some reports also describe the presentation as cold abscesses or eyelid skin ulcers. To our knowledge, only two previous reports have identified M. tuberculosis as the cause for diffuse eyelid edema.[1],[4]

Diagnosis of periocular tuberculosis is complex and requires a full workup, including a detailed history and physical examination, general laboratory testing, tuberculin skin test (TST) or serum IGRA, skin biopsy with histopathological analysis, and also sample culture or DNA amplification.[2]

TST has significant limitations owing to its low sensitivity and specificity. IGRA tests, such as QuantiFERON-TB Gold, present a good alternative, given the increased specificity and lack of cross-reactivity to BCG. IGRA tests are routinely used for screening for latent tuberculosis in immunocompromised patients but are also useful in the diagnosis or exclusion of active tuberculosis (with reported sensitivity around 89–91% in ocular tuberculosis).[5] Biopsy is crucial. The histological hallmark is the epithelioid granuloma with caseation necrosis, but tuberculosis forms part of the differential diagnoses of any chronic granulomatous inflammation.

The diagnosis of periorbital tuberculosis should be confirmed by identification of the bacilli in tissue samples. Detection of acid-fast bacteria is rapid but may be extremely difficult, and Ziehl–Neelsen staining is commonly negative. Mycobacterial culture remains the most reliable method,[1] however, culture sensitivity is low and often takes many weeks. Amplification of mycobacterial DNA by PCR is being increasingly used in the diagnosis of all forms of tuberculosis, given its higher specificity and sensitivity. In addition to being a rapid diagnostic test, only a small sample is needed, and formalin-fixed paraffin-embedded tissue is adequate for this method.[2]

This report presents a remarkably rare case of PCR-confirmed isolated periorbital tuberculosis, presumably originated in the reactivation of an old latent tuberculosis infection. Considering the atypical presentation of the case and the negative laboratory findings, tissue sampling was crucial in guiding further diagnostic workup. The authors highlight the importance of a thorough and exhaustive investigation in such cases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Bajaj DK, Srivastava A, Kushwaha RA, Joshi A, Pandey MK, Mishra P, et al. Two cases of eyelid tuberculosis – An uncommon presentation of ocular tuberculosis. Indian J Tuberc 2017;64:47-9.  Back to cited text no. 1
Sheu SJ, Shyu JS, Chen LM, Chen YY, Chirn SC, Wang JS. Ocular manifestations of tuberculosis. Ophthalmology 2001;108:1580-5.  Back to cited text no. 2
Salam T, Uddin JM, Collin JR, Verity DH, Beaconsfield M, Rose GE. Periocular tuberculous disease: Experience from a UK eye hospital. Br J Ophthalmol 2015;99:582-5.  Back to cited text no. 3
Castillo Varona, Eduardo, Toledano Grave de Peralta, Yanara. (2011). Tuberculosis palpebral en un anciano. MEDISAN, 15(2), 248-251.  Back to cited text no. 4
Agrawal R, Grant R, Gupta B, Gunasekeran DV, Gonzalez-Lopez JJ, Addison PK, et al. What does IGRA testing add to the diagnosis of ocular tuberculosis? A Bayesian latent class analysis. BMC Ophthalmol 2017;17:245.  Back to cited text no. 5


  [Figure 1], [Figure 2]


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