Primary eyelid involvement may present as redness, swollen eyelid, chronic conjunctivitis, chalazion, preseptal cellulitis, tarsal necrosis, or a surgical complication following blepharoplasty surgery [14–16]. It can also be the initial presentation of orbital, adnexal, or cutaneous tuberculosis [17]. In a case report, authors reported a patient of tuberculosis presenting simultaneously with eyelid swelling and thyroid enlargement [18].

Involvement of the lacrimal gland is rare and lacrimal sac is even rarer. The former was first described by Abadie (1881), and since then many cases have been reported [19]. Over a period of 20 years, 14 cases of tuberculosis involving the orbit and lacrimal gland have been described in a case series [20]. Patients present with abaxial proptosis with a mass in the region of the lacrimal gland, ptosis, and limitation of ocular movements. Lacrimal gland involvement usually occurs in association with periostitis/osteomyelitis which usually affects the lateral orbital wall or with involvement of the orbital soft tissue/abscess [21, 22]. Isolated lacrimal gland involvement has also been reported. According to the author, the isolated form is usually of the sclerotic type and rarely of the caseous type [19, 20].

Tubercular infection of the lacrimal drainage system (sac and nasolacrimal duct) is very rare [4, 23]. The sac infection usually occurs secondary to nasolacrimal duct infection [24–26]. The latter commonly presents with epiphora because of which the diagnosis might get delayed resulting in spread of infection to adjacent structures like sac, conjunctiva, nasal cavity, sinuses with or without its destruction, or overlying skin infection (lupus vulgaris) [23, 27]. Rarely, extensive involvement of the conjunctiva, skin, eyelid, and cheek heals with significant facial deformity and ocular surface damage. Systemic involvement has also been reported [28].

The maxillary sinus is most commonly involved. Patients generally present with proptosis and/or discharging fistula in the sinus region, palpable mass, epistaxis, etc [3].

An estimated 1–2% of all tuberculosis cases have skin involvement. The lesion typically occurs around the nose followed by the arms, legs, and trunk. The periorbital skin lesions can involve the eyelid skin and conjunctiva and may also present with cicatricial ectropion or bony involvement. Lupus vulgaris is the commonest form of cutaneous tuberculosis seen in India, followed by tuberculosis verrucosa cutis and scrofuloderma. The former is characterized by slowly enlarging plaque with slightly elevated borders and central atrophy.

Other presentations are preseptal cellulitis, ulcerated skin nodule, erythematous plaque, or pigmented nodular lesion mimicking basal cell carcinoma [17, 28, 29]. Alternate differential diagnoses for skin tuberculosis are mucocutaneous leishmaniasis, pyogenic granuloma, fungal infection, treponematosis of the skin, sarcoidosis, neoplastic ulcer, Wegener’s granulomatosis, and midline granuloma [28]. Because it masquerades many skin lesions, the diagnosis may not be established until the disease is biopsied or the patient presents with a full-blown picture.

There is an increase in prevalence of pulmonary as well as extrapulmonary tuberculosis due to an epidemic of human immunodeficiency virus (HIV) infection and the greater use of different types of immunosuppressive therapies [2, 30]. In human immunodeficiency virus (HIV)-positive patients, extrapulmonary tuberculosis accounts for up to 53–62% cases of tuberculosis [2]. These patients are at markedly increased risk for primary or reactivation tuberculosis and for second episode of tuberculosis from exogenous reinfection. Among adult patients with HIV, the incidence of ocular involvement is high, varying from 50% to 90%. Tuberculosis of orbit in such patients is extremely rare. Authors reported a case with proptosis because of tuberculosis as the initial manifestation in a HIV-positive patient [31].

Common fungal infections are zygomycetes which have two orders of organisms that infect humans, Mucorales and Entomophthorales. Mucorales include Rhizopusa and Mucor, which are angioinvasive and lead to acute infection in immunocompromised patients, while Entomophthorales include Basidiobolus ranarum, Conidiobolus incongruus, and Conidiobolus coronatus; these are not angioinvasive but invade subcutaneous tissue and cause chronic infection in immunocompetent patients. Presence of secondary infection in a tubercular lesion is seen in the pulmonary site, but its coexistence with fungal lesion is a rare entity. Orbital tuberculosis with coexisting fungal infection is extremely rare and leads to a diagnostic dilemma. Such infections are seen in immunocompromised patients such as diabetics, blood malignancies, neutropenia, AIDS, malnutrition, or anemic patients. A case of coinfection in the skull base and orbit by Mycobacterium tuberculosis and Aspergillus flavus, in a poorly controlled diabetes mellitus patient, was reported for the first time in 2014 [32]. In another case study, authors reported a case of disseminated tuberculosis with Conidiobolus coronatus infection presenting as orbital cellulitis in an adolescent [33].

Patients presenting with orbital and periorbital manifestations of tuberculosis may have symptoms of active tuberculosis elsewhere. Detailed local and systemic examination is a must for the diagnosis in all suspicious/atypical cases as well as cases not responding to conventional treatment. CT scan of the head and orbit is done to know the extent of lesion, bony, and intracranial involvement. Blood examination for raised ESR values and lymphocytosis should be done. Mantoux test helps to know the hypersensitivity to tubercular protein and is considered to be significantly raised if induration is more than 15 mm and borderline if it is between 10 and 15 mm. However, Mantoux test has a limited value in adults in endemic countries like India. In a study, a positive Mantoux test was found in 67–90% of healthy individuals [34]. However, it may be of use in children aged 5 years and below.

As orbital disease is essentially a paucibacillary condition, so in all cases, biopsy specimen for histopathological and/or microbiological examination is mandatory. Open or fine needle aspiration biopsy is done in most of the cases (Fig. 14.1c). Demonstration of tubercle bacilli on Ziehl-Neelsen staining is the most rapid way of detection of infection. However, according to a review, bacilli were seen only in 18 out of 59 cases of orbital tuberculosis [3]. Histopathologically, it is a granulomatous inflammation (epithelioid granulomas with Langerhans giant cells) with caseation necrosis. Immunohistochemical staining using mycobacterial antigen MPT64 may provide supportive evidence. Polymerase chain reaction is a rapid, nucleic acid amplification technique for the diagnosis. It has high specificity (>90%) for pulmonary and extrapulmonary disease with variable sensitivity [35, 36]. Culture of mycobacteria is considered the gold standard for confirmation of infection. In paucibacillary form of tuberculosis, such as orbital tuberculosis, limited studies are available on culture sensitivity and specificity, but according to a major review on orbital tuberculosis, 19 out of 79 cases yielded a positive culture [3]. In pulmonary tuberculosis , the sensitivity of culture technique is 80–85% with a specificity of 98% [35]. Chest X-ray and/or chest CT scan in many cases shows features of active or healed tubercular lesions. In a review on orbital tuberculosis, chest radiographs were consistent with pulmonary disease in 53% cases [3]. Sputum examination is required in cases with clinical suspicion of chest infection. Immunoglobulin release assay (IGRA) , fluorescence quantitation PCR (FQ-PCR) , and colloidal gold assay are the newer tests which help in the confirmation of diagnosis.

Generally more than one test is necessary for the confirmation of diagnosis. In a case series reported from our center, drainage and curettage was done for five patients, needle drainage of fluid was done in one patient, and in two patients local debridement was done. Polymerase chain reaction for tuberculosis was positive in four cases, and acid-fast bacilli (AFB) were isolated on culture in three cases. On histopathology, six cases had granulomatous inflammation with caseating necrosis in one, though AFB could not be found [11]. In another report from our country, in all seven patients with tubercular preseptal cellulitis, an evidence of underlying active and healed focus was present. In addition to this, a strongly positive Mantoux test with necrosis reaction in one case, acid-fast bacilli from the discharging pus in one case, positive family history in one case, and smear positive for AFB in one case helped in establishing the diagnosis [12]. In a separate case series of six patients, all patients had chronic granulomatous inflammation with caseation necrosis, polymerase chain reaction was positive in two patients, acid-fast bacilli were found in two patients, culture was negative in all, and chest radiograph was normal in all the patients [5].