Volume 22 Number 1 / February 2018
fusiform enlargement of right lateral rectus muscle without
involvement of the tendon. Their patient showed improve-
ment with steroid treatment. In our case, the diplopia and
ocular alignment at the primary gaze improved after treat-
ment for Graves disease. However, the ocular motility
showed worsening of abduction in the right eye and adduc-
tion in the left eye. These changes of ocular motility might
account for the improvement of exotropia.
It is well known that patients with TED have a greater
incidence of myasthenia gravis (MG); both entities repre-
sent autoimmune diseases.1,7,10 Vargas and colleagues10 re-
ported patients with TED who showed exotropia due to
concomitant MG. Chen and colleagues7 suggested that
MG may develop many years after the onset of Graves dis-
ease, and exotropia is rare in patient with TED. They rec-
ommended that the development of an exotropia in a
patient with TED should alert clinicians to the possible
development of MG. In our case, the possibility of
concomitant MG was ruled out, because the patient did
not have ptosis characteristic features of MG, and his
symptoms were not associated with diurnal variations or
correlated with fatigue. Moreover, the anti-acetylcholine
receptor antibody test was negative. However, the patient
will be closely followed because of the possibility of
concomitant MG.
Literature Search
PubMed and Google Scholar were searched on June 1,
2017, without language or data restrictions, using the
following terms singly and in combination: thyroid eye
disease, Graves disease, strabismus, exotropia, and diplopia.
References
1. Biousse V, Newman NJ. Neuro-Ophthalmology Illustrated. 2nd ed.
New York: Thieme; 2016:321-465.
2. Mizen T. Thyroid eye disease. Semin Ophthalmol 2003;18:243-7.
3. Schotthoefer EO, Wallace DK. Strabismus associated with thyroid
eye disease. Curr Opin Ophthalmol 2007;18:361-5.
4. Gruters A. Ocular manifestations in children and adolescents with
thyrotoxicosis. Exp Clin Endocrinol Diabetes 1999;107:172-4.
5. Krassas GE. Thyroid eye disease in children and adolescents—new
therapeutic approaches. J Pediatr Endocrinol Metab 2001;14:
97-100.
6. Uretsky SH, Kennerdell JS, Gutai JP. Graves’ ophthalmopathy in
childhood and adolescence. Arch Ophthalmol 1980;98:1963-4.
7. Chen CS, Lee AW, Miller NR, Lee AG. Double vision in a patient
with thyroid disease: what’s the big deal? Surv Ophthalmol 2007;52:
434-9.
8. Erdurmus M, Celebi S, Ozmen S, Bucak YY. Isolated lateral rectus
muscle involvement as a presenting sign of euthyroid Graves disease.
J AAPOS 2011;15:395-7.
9. Roberts CJ, Murphy MF, Adams GG, Lund VJ. Strabismus following
endoscopic orbital decompression for thyroid eye disease. Strabismus
2003;11:163-71.
10. Vargas ME, Warren FA, Kupersmith MJ. Exotropia as a sign of myas-
thenia gravis in dysthyroid ophthalmopathy. Br J Ophthalmol 1993;
77:822-3.
Journal of AAPOS
Raab et al 73
Lacrimal gland abscess in a
child as a rare
manifestation of
IgG4-related disease
Edward L. Raab, MD, JD,a,b
Hamideh S. Moayedpardazi, MD,a
Steven M. Naids, MD,a Alan H. Friedman, MD,a,c
and Murray A. Meltzer, MDa
Dacryoadenitis is unusual in children, and noninfectious causes can
be manifestations of serious undiagnosed systemic conditions. This
report brings further attention to this rarely-encountered condition
and emphasizes its association with IgG4-related disease, a group
of inflammatory disorders of high current interest whose spectrum
of manifestations continues to evolve. The pediatric ophthalmolo-
gist could be in the position of identifying a patient’s serious and
previously unappreciated illness.
Case Report
A 3-year-old boy presented at the Emergency Department
of the Icahn School of Medicine at Mount Sinai for care of
orbital cellulitis, suspected because of worsening swelling
and redness around his right eye of 2 weeks’ duration.
His mother stated that he was not in pain but that the upper
eyelid now felt “hard” and was “drooping.” There was a
history of recurrent episodes of swelling around the right
eye since the child was 9 months of age.
On examination, near visual acuity was 20/20 in both
eyes. Pupil sizes were equal, with no afferent defect. Color
vision was intact. There was limited abduction and eleva-
tion of the right eye. The globe was displaced downward
and forward, and there was prolapse of reddish tissue
from the lateral aspect of the upper conjunctival fornix.
Anterior segment structures were normal, and the optic
disk and posterior pole were unremarkable. The left eye
and adnexae were normal in all respects. The child was
active, afebrile, and with no evidence of respiratory or other
infection. Initial laboratory study was remarkable only for a
white blood cell count of 16,700/cu mm (normal range,
5,300–12,500/cu mm) and an elevation of C-reactive
Author affiliations: Departments of aOphthalmology, bPediatrics, and cPathology, Icahn
School of Medicine at Mount Sinai, New York, New York
Submitted April 29, 2017.
Revision accepted August 7, 2017.
Published online December 27, 2017.
Correspondence: Edward L. Raab, MD, JD, Department of Ophthalmology, Icahn School
of Medicine at Mount Sinai, 1 Gustave Levy Place, Box 1183, New York, NY 10029
(email: eraabmdjd@aol.com).
J AAPOS 2018;22:73-75.
Copyright Ó 2018, American Association for Pediatric Ophthalmology and
Strabismus. Published by Elsevier Inc. All rights reserved.
1091-8531/$36.00
https://doi.org/10.1016/j.jaapos.2017.08.013
74 Raab et al
FIG 1. Magnetic resonance imaging with contrast showing right
lacrimal gland abscess cavity (A) and flattening of the globe (B) by
enlarged right lacrimal gland.
FIG 2. Lacrimal gland abscess cavity opened showing purulent con-
tents.
protein (30.4 mg/l; normal, 0.00–0.5 mg/l), both of which
subsided. A blood culture obtained on admission showed
no growth after 4 days.
Magnetic resonance imaging (MRI) with contrast re-
vealed a cavitary abscess in an enlarged right lacrimal
Volume 22 Number 1 / February 2018
FIG 3. A, Biopsy specimen, showing lymphoplasmacytic infiltration,
fibrosis, and vascular obliteration (hematoxylin-eosin, original magni-
fication 400). B, Positive staining for IgG4 (B).
gland, without extension to the subperiosteal space or
cavernous sinus; flattening and indentation of the lateral
aspect of the globe were present. The brain and sinuses
were not involved (Figure 1). With neither deterioration
nor improvement of his clinical condition by the third
day of treatment with intravenous clindamycin and despite
spontaneous purulent drainage from the superior fornix,
surgery was performed via an anterior approach. A large
amount of purulent material was encountered within the
abscess (Figure 2) and was removed. A culture showed
Staphylococcus aureus.
Because one of the treating physicians (MAM) had
experience with the group of conditions known as
IgG4-related disease, and given the history of recurrent
right periorbital swelling since infancy, a biopsy of the
thickened abscess wall was obtained for IgG4 staining.
The incision was closed in layers after copious irriga-
tion of the cavity with gentamycin solution. The post-
operative course was uneventful, and the patient
was discharged after 2 days to continue clindamycin
orally for 2 weeks. As of the 14th postoperative day,
there was substantial resolution of swelling, with
partially improved abduction and elevation of the eye.
The biopsy showed an epithelial lining as well as
fibrosis and chronic nongranulomatous inflammation
Journal of AAPOS
Volume 22 Number 1 / February 2018
(Figure 3A). Lacrimal acini were present. The excised
tissue contained cells that stained positively for
IgG4 (Figure 3B). Because of noncompliance with
several attempts to carry out our plan to obtain rhe-
umatology consultation and to follow the outcome
of this child’s illness, we cannot report further informa-
tion.
Discussion
Causes of acute and subacute dacryoadenitis across all age
groups include infections by a wide range of agents.
Noninfectious causes, more typically in adults, include thy-
roid ophthalmopathy, Wegener’s granulomatosis, and
sarcoidosis (see eAppendix).
The diagnosis is readily suggested by upper eyelid
swelling that is most prominent laterally, an S-shaped
appearance of the eyelid margin, and visible swelling and
prolapse of the palpebral lobe, as our patient demon-
strated.1 MRI is the preferred confirming study. Flattening
of the lateral aspect of the eye from pressure by the
enlarged gland is a highly reliable sign.1 The characteristics
on imaging substantially eliminate from consideration
rhabdomyosarcoma, vascular malformations, and metasta-
tic disease. Contrast enhancement has been advocated as
indispensable in order to show abscess formation
(Figure 2).2
Infectious agents reach the lacrimal gland most typically
by spread from the adjacent paranasal sinuses. Blood-borne
spread, usually from respiratory infections or extension
from the skin or ocular surface via the lacrimal ductules
are additional routes. The most serious sequel of dacryoa-
denitis, although unusual in children, is purulent abscess
formation. which has occurred more prominently with
the emergence of methicillin-resistant staphylococcus
aureus.3
When intensive treatment with intravenous antibiotics
has been ineffective, and vision remains threatened, surgi-
cal drainage is required. Culture studies to dictate therapy
are of limited value, because they are often negative both in
blood and in the abscess contents.
The history of recurrent eyelid swelling since infancy
in this patient suggested the possibility of something
other than a local infection, a suspicion confirmed by ex-
amination of the excised abscess wall. Since an IgG4-
related entity was not suspected at the time of the pa-
tient’s presentation, blood levels of this indicator were
not obtained. However, the accumulating literature indi-
cates that demonstration in tissue is a more persuasive
determining criterion.4,5 C-reactive protein, although
elevated in this patient, reflects inflammation in general
and is often normal in IgG4-related disease. By
consensus, the characteristic histologic features are lym-
Journal of AAPOS
Raab et al 75
phoplasmacytic infiltration, storiform (irregularly
whorled) fibrosis, and obliterative phlebitis, as demon-
strated in our case.6
The classification, multiple clinical settings and char-
acteristics, and diagnostic features of IgG4-related dis-
orders continue to evolve.6-10; Appendix Serologic criteria
and the number or percentage of IgG4-positive cells in
a biopsy necessary for this diagnosis, for example, have
been organ- or tissue type–specific and variably re-
ported.6 This entity can cause fibrosis from inflamma-
tion and often irreversible damage to most body
tissues. Therefore, early recognition and prompt
treatment are critical. Prednisone has been effective as
first-line therapy, with rituximab as an alternative
steroid-sparing agent. At the minimum, referral for
rheumatology investigation is an important adjunctive
measure. Occurrence in the orbit, especially bilaterally,
could indicate the presence of more widespread
involvement,8 placing the pediatric ophthalmologist in
the role of “first responder” to identification and treat-
ment. IgG4-related disease should be considered in the
differential diagnosis of orbital masses or inflamma-
tions, especially when recurrent, in the pediatric age
group.
References
1. Sayani A, Smith DE. Clinical recognition and management of atypical
dacryoadenitis. Clin Pediatr (Phila) 2015;54:956-60.
2. Parvizi N, Choudhury N, Singh A. Complicated periorbital
cellulitis: case report and literature review. J Laryng Otol 2012;126:
94-6.
3. Mathias MT, Horsley MB, Mawn LA, et al. Atypical presentations of
orbital cellulitis caused by methacillin-resistant stapylococcus aureus.
Ophthalmology 2012;119:1238-43.
4. Teo L, Seah LL, Choo CT, Chee SP, Chee E, Lool A. A survey of the
histopathology of lacrimal gland lesions in a tertiary referral center.
Orbit 2013;32:1-7.
5. Andrew NH, McNab AA, Delva D. Review of 268 lacrimal gland
biopsies in an Australian cohort. Clin Exp Ophthalmol 2015;43:
5-11.
6. Karim F, Loeffen J, Bramer W, et al. IgG4-related disease: a system-
atic review of this unrecognized disease in pediatrics. Pediatr Rheu-
matol Online J 2016;14:18.
7. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al.
Consensus statement on the pathology of IgG4-related disease.
Mod Pathol 2012;25:1181-92.
8. Wu A, Andrew NH, McNab AA, Selva D. Bilateral IgG4-related
ophthalmic disease: a strong indication for systemic imaging. Br J
Ophthalmol 2016;100:1409-11.
9. Cheuk W, Yuen HKL, Chan JKC. Chronic sclerosing dacryoadenitis:
part of the spectrum of IgG4-related sclerosing disease? Am J Surg
Pathol 2007;31:643-5.
10. Umehara H, Okazaki K, Masaki Y, et al., Research Program for
Intractable Disease by Ministry of Health, Labor and Welfare
(MHLW) Japan G4 team. A novel clinical entity, IgG4-related dis-
ease (IgG4RD); general concept and details. Mod Rheumatol 2012;
22:1-14.
Volume 22 Number 1 / February 2018
eAppendix. Supplemental references
1. Andrew NH, Kearney D, Sladden N, et al. Idiopathic dacryoadenitis:
clinical features, histopathology, and treatment outcomes. Am J
Ophthalmol 2016;163:148-153.e1.
2. Chakaborti C, Biswas R, Mondal M, Mukhopadhya U, Datta J.
Tuberculous dacryoadenitis in a child. Nepal J Ophthalmol 2011;
3:210-13.
3. Cheuk W, Yuen HK, Chan AC, et al. Ocular adnexal lymphoma
associated with IgG4 chronic sclerosing dacryoadenitis: a previously
undescribed complication of IgG4-related sclerosing disease. Am J
Surg Pathol 2008;32:1159-67.
Journal of AAPOS
Raab et al 75.e1
4. Goold LA, Madge SN, Au A, et al. Acute suppurative bacterial dacryoa-
denitis: a case series. Br J Ophthalmol 2013;97:735-8.
5. Kalapesi FB, Garrott HM, Moldovan C, Williams M, Ramanan A,
Herbert HM. IgG4 orbital inflammation in a 5-year-old child present-
ing as an orbital mass. Orbit 2013;32:137-40.
6. Krishna N, Lyda W. Acute suppurative dacryoadenitis as a sequel to
mumps. Arch Ophthalmol 1958;59:350-51.
7. Patel N, Khalil HM, Amirfeyz R, Kaddour HS. Lacrimal gland abscess
complicating acute sinusitis. Int J Pediatr Otorhinolaryng 2003;67:917-19.
8. Sen DK. Acute suppurative dacryoadenitis caused by cysticercus
cellulosa. J Pediatr Ophthalmol Strabismus 1982;19:100-102.