Gangadhara SundarDr. Sundar graduated from the Madras Medical College. Following his basic ophthalmology training in India, he received his postgraduate ophthalmology residency and fellowship training in Ophthalmic Plastic & Reconstructive Surgery and Ocular Oncology at the Henry Ford Hospital, Detroit. With an extensive multinational multiethnic multispeciality practice exposure and patient experience, he currently serves as Head, Orbit & Oculofacial Surgery, Ophthalmic Oncology at the National University Hospital, Singapore, committed to clinical research, education of residents and fellows with national, regional, and international outreach. His interests include orbital inflammatory diseases including thyroid eye disease; minimally invasive orbital, lacrimal, and oculofacial surgery; orbito-facial trauma in addition to aesthetic oculofacial surgery and is a strong proponent of multidisciplinary approaches to complex orbito-facial disorders.
Inflammation of the lacrimal gland is a relatively common orbital inflammatory disorder, both in children and adults. Like in most clinical inflammatory syndromes, differentiation between an infectious and noninfectious etiology is important as both the treatment and the prognosis depend on the same. We shall herewith cover the various aspects of diagnostic and therapeutic challenges in the management of dacryoadenitis.
Dacryoadenitis is any acute, subacute, or chronic inflammatory condition of the lacrimal gland . While it is commonly attributed to the main lacrimal gland, the accessory lacrimal glands may also be affected. Inflammations may be either of infectious or noninfectious etiology, and when both have been ruled out, infiltrative and masquerade syndromes have to be considered.
The lacrimal secretory system is comprised of the main and accessory lacrimal glands. Rarely, ectopic cell rests of the lacrimal gland may also be present which may be a source of lacrimal secretory pathology. The main lacrimal gland is an almond-shaped structure resting in the lacrimal gland fossa of the frontal bone along the superotemporal quadrant of the orbit behind the orbital rim . The palpebral lobe extends anteriorly towards the upper and outer quadrant of the upper eyelid and separated from the orbital lobe by the lateral horn of the aponeurosis of the levator palpebrae superioris. The main lacrimal gland drains into the superotemporal and lateral fornix through 10–15 ductules, which can be identified on slit-lamp examination. The accessory lacrimal glands are mainly comprised of the glands of Krause and Wolfring. The glands of Krause are present primarily along the superior fornix (approximately 42 in number) and minimally along the inferior fornix (around eight), draining directly into the fornices mainly laterally. The glands of Wolfring are present along the superior and inferior tarsal margins (5–10). Accessory lacrimal glands may also be present in the caruncle and the lateral forniceal areas.
Etiology and Classification
Most inflammatory conditions of the lacrimal gland are either of viral etiology or of nonspecific etiology . Acute suppurative infection of the lacrimal gland is rare and, when present, should prompt a search for an underlying systemic etiology, significant systemic immunocompromise, or in endemic areas tuberculosis as well. Isolated fungal infections are extremely rare and may be seen only in the immunocompromised patients. Parasitic infestations are not uncommon in endemic areas, the most common being cysticercosis and rarely hydatidosis. When infectious etiologies are presumed less likely or have been ruled out, noninfectious causes of lacrimal gland inflammation should be considered. As a general rule, all noninfectious inflammations of the lacrimal gland are of “specific” etiology until proven otherwise. When chronic or recurrent dacryoadenitis is present, either unilateral or bilateral, a tissue diagnosis is often useful especially in ruling out lymphoproliferative disorders and other rare pathologic entities.
An outline of the various etiologies is shown in Table 38.1.
Etiological classification of dacryoadenitis
Thyroid eye disease 
Lymphoproliferative disorders 
Malignant lacrimal gland tumors, e.g., adenoid cystic carcinoma, mucoepidermoid carcinoma
Parasitic, e.g., cysticercosis , hydatidosis, schistosomiasis
Protozoan, e.g., acanthamoeba 
Nonspecific orbital inflammatory syndrome (idiopathic dacryoadenitis)
Viral dacryoadenitis presents typically in a child or young adult  with either a unilateral or bilateral acute onset of swelling, redness, and induration with pain on palpation over the upper outer eyelid (Fig. 38.1). Fever, malaise, or other constitutional signs and symptoms from systemic viral infection may be present. Although symptoms may be unilateral, not infrequently patients may have bilateral features either clinically or radiologically. Overlying preseptal swelling and underlying orbital signs of limitation of ocular motility and chemosis with mucoid discharge may be present. In the pre-MMR (Measles, Mumps, Rubella) universal vaccination era, associated features of parotitis were not uncommon pointing towards mumps virus as a possible etiological agent.
Typical presentation of viral dacryoadenitis in a young adult
Bacterial dacryoadenitis may have a similar presentation but usually unilateral with much more severe pain, chemosis, and limitation of ocular motility (Fig. 38.2). Commonly caused by staphylococcus aureus or streptococcus, the typical patient is an elderly or immunocompromised patient with systemic bacteremia as the infection is often endogenous. More commonly, spread from an overlying preseptal cellulitis (scratch wound infections or hordeolum internum or externum) may occur in immunocompetent children and young adults. A high degree of suspicion for atypical infections including tuberculosis (typical or atypical mycobacteria) should be considered in subacute and in high-risk cases. Rarely, they may progress towards an abscess formation  with a throbbing sensation, mass effect, and loculation seen on orbital imaging.
Bacterial dacryoadenitis of the left orbit
Parasitic infestations are not uncommon in the South Asian, African, and South American continents where they may be endemic. Cysticercosis is one of the most common orbital inflammatory diseases which may present as a dacryoadenitis, and usually unilateral (Fig. 38.3). It is only upon clinical suspicion, serological testing, and typical findings of a localized inflammation with a central cystic space and a scolex when present that helps clinch a diagnosis . Hydatidosis may present as large multiloculated thick-walled cystic lesions involving any part of the orbit and has classic radiological features with absent systemic disease.
T2-weighted MR image showing cysticercosis of the right lacrimal gland
By far, the most common of all noninfectious inflammatory lesions of the lacrimal gland are “nonspecific dacryoadenitis” and often form a distinct subsect of nonspecific orbital inflammatory syndromes (NSOIS), previously termed “pseudotumor” or “idiopathic dacryoadenitis” . However, they are diagnoses of exclusion, only after a complete workup for possible underlying systemic autoimmune and vasculitic disorders has been ruled out. Whenever possible a tissue diagnosis should be performed to confirm the diagnosis. Nonspecific dacryoadenitis may present in all age groups (Fig. 38.4a, b) and may be either unilateral or bilateral, typically with pain and the absence of systemic signs of either bacterial or viral infection. Not infrequently they may present as recurrent dacryoadenitis or a chronic inflammatory lesion with or without a mass effect. More commonly they are diagnosed based on limited or poor response to conventional treatment with antibiotics or anti-inflammatory agents and a dramatic response to systemic corticosteroids.
(a) Idiopathic dacryoadenitis pretreatment. (b) Idiopathic dacryoadenitis post-treatment
Lymphoproliferative disorders may also present as “nonspecific” inflammation, with recurrent attacks of unilateral or bilateral swelling in the region of the lacrimal gland  (Fig. 38.5a–c). Hence all patients presenting with dacryoadenitis or orbital inflammatory disease should be presumed to have a specific inflammatory or infiltrative pathology until proven otherwise. Such patients may also have regional or systemic lymphadenopathy which may raise level of suspicion.
(a) Bilateral lacrimal gland enlargement from B-cell lymphoma in a patient referred for ptosis correction. (b) Bilateral lacrimal gland enlargement on CT scan. (c) Lacrimal gland biopsy
Common differential diagnosis include the following:
Preseptal cellulitis secondary to underlying hordeolum internum (acute meibomitis) or hordeolum externum (stye)
Early orbital cellulitis
Ruptured dermoid cyst
Thyroid eye disease
Primary lacrimal gland neoplasms: pleomorphic adenoma , adenoid cystic carcinoma, mucoepidermoid carcinoma, and ductal carcinoma (Fig. 38.6a, b)
(a) Ductal carcinoma of lacrimal gland simulating dacryoadenitis and orbital inflammation. (b) Coronal MRI showing enhancing lesion of the left lacrimal gland
Diagnosis of dacryoadenitis is essentially based on a high level of clinical suspicion based on the history, review of systemic symptoms, and clinical examination. Investigations are performed either to confirm or rule out the possible diagnosis and other differential diagnosis as listed above.
Laboratory investigations: A conjunctival swab of the discharge may help with early detection of bacterial infection and thus direct specific treatment. Bacterial sensitivity for antibiotic resistance may be important. Basic tests should include a complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), syphilitic titres (VDRL, TPHA), chest x-ray (TB, sarcoidosis, etc.), and Mantoux testing. When bacterial dacryoadenitis is suspected especially with systemic symptoms, a blood culture with sensitivity to antibiotics  may also be useful. When parasitic infestations are suspected, anti-cysticercosis antibodies may complement imaging findings.
When a noninfectious etiology is suspected, a complete inflammatory workup is often indicated. Based on level of suspicion of underlying specific autoimmune vasculitic disorders, the following investigations may be considered: rheumatoid factor (RF), anti-nuclear antibody (ANA), Sjogren’s antibody testing (anti-SS-A and anti-SS-B, as a part of an extractable nuclear antibodies (ENA) panel), anti-alpha-fodrin antibody (in juvenile Sjogren’s syndrome), anti-neutrophilic cytoplasmic antibody (ANCA), and anti-proteinase 3 (anti-PR3 antibodies). Tests for sarcoidosis include serum amyloid A (SAA), soluble interleukin-2 receptor (sIL-2R), lysozyme, angiotensin-converting enzyme (ACE), and glycoprotein KL-6.