Journal of Crohn's and Colitis (2008) 2, 337–342
a v a i l a b l e a t w w w. s c i e n c e d i r e c t . c o m
SHORT REPORT
Recurrent posterior scleritis and orbital myositis as
extra-intestinal manifestations of Crohn's disease:
Case report and systematic literature review
Emma L. Culver a , John F. Salmon b , Peggy Frith b , Simon P.L. Travis a,⁎
a
b
Department of Gastroenterology, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK
Department of Opthalmology, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK
Received 22 March 2008; received in revised form 23 June 2008; accepted 27 June 2008
KEYWORDS
Crohn's disease;
Orbital myositis;
Posterior scleritis;
Extra-intestinal
manifestation;
Cyclophosphamide
Abstract
Background: Ocular episcleritis and uveitis are well-recognised extra-intestinal manifestations
of Crohn's disease. Orbital myositis is rare: to our knowledge it has been associated with Crohn's
disease in thirteen cases. Posterior scleritis, orbital myositis and Crohn's disease have been
reported as coexisting in only two cases.
Methods and results: We describe a third case, that of a 31-year old female with Crohn's colitis
for 8 years, complicated by enteropathic arthritis and pyoderma gangrenosum. She presented
with intense and intractable periorbital pain, particularly at night and worse on eye movements.
B-scan ultrasonography confirmed posterior scleritis and treatment with high dose oral steroids
(up to 60 mg prednisolone) was initially effective, but subsequently failed to control the
inflammation. There was only a partial response to infliximab. Five months after presentation,
diplopia developed, with failure of abduction of the left eye. MRI scan of the orbits confirmed
orbital myositis involving the left lateral and medial rectus muscles. Pulsed intravenous
methylprednisolone and six cycles of intravenous cyclophosphamide over a three month period
resulted in complete resolution of inflammatory symptoms.
Conclusions: This case highlights a rare combination of ocular abnormality secondary to Crohn's
disease and reports successful resolution with aggressive immunosuppressive therapy.
© 2008 European Crohn’s and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
1. Introduction
⁎ Corresponding author. Department of Gastroenterology, Level 5,
John Radcliffe Hospital, Oxford, OX3 9DU, UK. Tel.: +44 01865
228753; fax: +44 01865 228763.
E-mail addresses: [email protected],
[email protected] (S.P.L. Travis).
Extra-intestinal manifestations of Crohn's disease (CD),
characterised by inflammatory conditions outside the digestive tract, occur in about 15% of patients.1 They can relate to
the underlying disease activity or be independent of it.
Manifestations can coexist, with up to 30% of patients having
multiple; the presence of one increasing the risk of others.1
1873-9946/$ - see front matter © 2008 European Crohn’s and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.crohns.2008.06.002
338
E.L. Culver et al.
Table 1
Case reports of orbital myositis in association with Crohn's disease
Age/sex
Initial
Ocular
Distribution Associated EIM
presentation involvement of CD
or other disease
Unknown Unknown
14 F
Ocular
Unknown
Bilateral
LR, MR
Unknown
Terminal
ileal
Unknown
FH CD
HLA-B15, B13
17 F
Ocular
Unilateral
SR
Colonic
15 F
Ocular
Terminal
ileal
12 F
Ocular
Bilateral
Muscle
cones
Bilateral
FH DM, RA
HLA-B8, B22
HLA-BW6 HLA-CW3
HLA-DR3 + 4 HLA-MND.
FH CD
Ileocolonic
38 F
GI
Unilateral
Ileocolonic
44 M
GI
Unilateral
SR
Ileocolonic
12 M
GI
Bilateral
LR
Ileocolonic
48 F
Ocular
Bilateral
Ileocolonic
RM/RL
54 F
GI
34 F
GI
Bilateral
MR
Unilateral
Ileal
Ileocolonic
MR
27 F
Ocular
Unknown Unknown
31 F
GI
Bilateral
LR
Colonic
Unknown
Unilateral
Unknown
Ileocolonic
MR, LR
Therapy
Recurrent Follow
Ref.
myositis Follow-up
Unknown
Oral antibiotics
CS
Ileal resection
IV Cefazolin
CS
Unknown
Yes
Unknown
3m
3
No
6m
5
No
3m
6
Yes
6m
7
No
10 wk
8
No
3m
9
Yes
2m
10
No
1 yr
11
Yes
1 yr
12
Yes
27 m
13
Yes
27 m
13
Unknown
Yes
Unknown
9m
14
CS
Dexa
Diet
FH Graves, SLE, CD
CS
5-ASA
Anal fistula
Colectomy
Asthma
CS
Salz
None
IV Ceftriaxone
Orbital
exploration
CS
Cystic acne
CS
Salz
AZA
Partial
Ileo-colectomy
Oral antibiotics
Dacryoadenitis
NSAID
CS
FH DM, RA
Colostomy
Diet
Autoimmune haemolytic SB resection
anaemia. Splenectomy CS
Rectovaginal fistula
CS
MTX
Ileocolic
anastamosis
IFX
Scleritis
CS
MTX
AZA/MP
Orbital
triamcinolone
RT
Colectomy
IFX
Scleritis
Unknown
Posterior scleritis
CS
AZA/MP
Arthropathy
MTX
MeP
Pyoderma
IFX
gangrenosum
CP
4
Current
case
Key: CS (high dose oral prednisolone); MeP (pulsed intravenous methylprednisolone); Dexa (IV dexamethasone); Salz (Salazopyrine); AZA/
MP (azathioprine/mercaptopurine); MTX (methotrexate); CP (cyclophosphamide); RT (radiotherapy); IFX (infliximab); MR (medial rectus
muscle); LR (lateral rectus); SR (superior rectus); RM/RL (rectus medialis and rectus lateralis); FH (family history); NSAID (non-steroidal
anti inflammatory).
Recurrent posterior scleritis and orbital myositis as extra-intestinal manifestations of Crohn's disease: Case report and
systematic literature review
339
Ocular manifestations have been reported in up to 10% of
patients with CD, including uveitis, episcleritis, scleritis and
chorioretinitis,2 although this is likely to be an overestimate
based on a referral population. Orbital involvement and
orbital myositis, defined as orbital inflammation confined to
one or more of the extraocular muscles, is exceptional. In a
review of 700 patients with inflammatory bowel disease (498
with CD), only one had orbital myositis (0.14%).3 Nine cases
have subsequently been reported, describing the association
of isolated orbital myositis with CD 3–12 (Table 1). The
coexistence of scleritis with orbital myositis in CD has been
documented in just two patients.13,14
We present the case of a patient with CD, recurrent
posterior scleritis and orbital myositis. This case highlights a
rare combination of ocular abnormalities secondary to CD
and describes the excellent response to aggressive immunosuppressive therapy.
2. Case report
A 23-year old woman presented in August 1999 with a fiveweek history of loose stools, urgency and abdominal pain. On
examination there was localised peritonism in the right iliac
fossa. Laboratory investigations revealed a normocytic
anaemia, raised inflammatory markers and thrombocytosis.
Terminal ileal CD was diagnosed at laparoscopy and
confirmed by small bowel enema. Colonoscopy showed no
evidence of distal colonic CD. She failed to settle with high
dose oral steroids and underwent ileocaecal resection with
anastamosis in November 1999. She remained asymptomatic
on no maintenance treatment for six months. In May 2000 she
presented with recurrent disease in the neoterminal ileum,
treated with corticosteroids. She was intolerant of thiopurines (azathioprine and 6-mercaptopurine). Methotrexate was
well tolerated and provided good control of her bowel
symptoms. She remained symptom-free for two years.
In October 2002 she presented with a peripheral asymmetric oligoarthritis, affecting the large joints of the lower
limbs. Her intestinal disease was active. Autoimmune screen
and rheumatoid factor were negative. Exacerbations of
arthritis were controlled by local intra-articular steroid
injections, systemic corticosteroids and increased doses of
methotrexate. Two years later, she developed skin ulceration
characteristic of pyoderma gangrenosum. Her bowel symptoms were quiescent. She was treated with infliximab (5 mg/
kg), which induced a positive response of up to two months.
Infliximab was continued every 2 months for 1 year. She
discontinued methotrexate in May 2005 as she wanted to
become pregnant.
In January 2006, she presented with a two-week history of
a painful right eye, particularly at night and exacerbated by
eye movement. Visual acuity was normal (6/6 right, 6/5 left).
There was mild chemosis and reproducible pain elicited by
horizontal gaze. Slit lamp and fundal examinations were
unremarkable. Hess chart analysis showed no evidence of
extraocular muscle defects. TSH was within the normal range
and thyroid autoantibodies were negative. A B-scan ultrasound of the right eye showed evidence of posterior scleral
thickening and a ‘Tsign’, typical of posterior scleritis (Fig. 1).
A non-steroidal (flurbiprofen 150 mg/day) was initiated, with
little relief. High dose oral steroids (prednisolone 40 mg/day)
Figure 1 B-scan ultrasound scans of the right eye A) inferior
B) VMAC (vertical macular) C) VON (vertical optic nerve) —
showing evidence of posterior scleral thickening, typical of
posterior scleritis.
were started and achieved an immediate response and were
tapered gradually over six weeks.
Over the next three months she experienced three
episodes of symptomatic posterior scleritis, affecting first
the right then the left eye, confirmed on B-scan ultrasonography. The pain responded to prednisolone 40 mg/day, but
recurred as the dose was reduced below 20 mg/day. Her
340
intestinal disease was active: colonoscopy demonstrated
moderately active segmental colitis with inflammation of the
ileocaecal anastamosis, confirmed by histopathology. She
was given infliximab for the intestinal activity, and the ocular
pain resolved immediately. She became pregnant later that
year and was given infliximab infusions in the second and
third trimesters for symptomatic intestinal disease. She had
an uncomplicated caesarian section and the healthy newborn
followed the usual vaccination programme.
In February 2007, she presented with a frontal headache
and severe left periorbital pain, resistant to high dose oral
steroids (60 mg prednisolone). Her intestinal disease was
active with increased bowel frequency and elevated inflammatory markers. Infliximab infusions (5 mg/kg) provided only
partial relief from periorbital pain (two weeks) and had no
impact on intestinal symptoms; they were subsequently
discontinued. The pain intensified and she developed
diplopia. On examination there was evidence of conjunctival
injection, chemosis and failure of abduction of the left eye.
Hess chart analysis revealed under-activity of the lateral
rectus and over-activity of the medial rectus muscle on
horizontal gaze. MRI of the orbits with gadolinium contrast
delineated enlarged left medial rectus and lateral rectus
muscles and their tendinous insertions consistent with
orbital myositis (Fig. 2). There was no localised inflammatory
mass and the right eye was unaffected.
She was admitted to a hospital for pulsed methylprednisolone (1 g on three consecutive days) and intravenous
cyclophosphamide (15 mg/kg every two weeks, six doses).
Oral corticosteroids were continued for twelve weeks
(prednisolone 15 mg/day). Within 1 h of the first intravenous
infusions her pain was markedly reduced and after the
E.L. Culver et al.
second infusion of cyclophosphamide her eye movements
returned to normal. Hess chart plots confirmed normal
activity of the muscles after treatment. After the third
infusion of cyclophosphamide she reported symptomatic
improvement in intestinal activity, there was no endoscopic
evaluation. There were no complications.
Two months after completion of the cyclophosphamide
infusions, she experienced a recurrence in symptomatic CD.
She was commenced on adulimumab (80 mg, 40 mg, 40 mg
subcutaneous injections at two two-week intervals) with
good effect. She has continued on maintenance treatment
every two weeks and remains in remission. At nine-month
follow follow-up there have been no further episodes of
orbital inflammation.
3. Systematic literature review
We used Pubmed database, Medline database and Ovid
search engine to identify studies and cases relevant to this
article. The keywords used in our search were orbital
myositis; ocular myositis; orbital pseudotumour; inflammatory bowel disease; Crohn's disease; ulcerative colitis.
Fifteen cases of orbital myositis associated with inflammatory bowel disease (thirteen with CD,3–14 two with UC 15,16)
have been reported (Table 1). In two of these cases, both
scleritis and orbital myositis were associated with CD.13,14
Three quarters (11/15 with details available) were female and
two thirds (10/15) had colonic or ileocolonic disease. In a
quarter (4/13 with CD) a family history of CD and other
associated autoimmune diseases were present. There was no
record of other extra-intestinal manifestations in the reports.
In half (6/13) ocular myositis presented before the
onset of CD. In half (7/13) the myositis was bilateral.
Visual compromise in the form of diplopia and blurred
vision affected three quarters (9/13), and in all but one
patient these features resolved with treatment. Persistent
diplopia and pain was reported in one patient at 27-month
follow-up.13 There were no incidences of blindness or
permanent visual loss.
4. Discussion
Figure 2 Magnetic resonance imaging of the orbits with
gadolinium contrast showing swelling of the medial and lateral
rectus muscles of the left eye. There is an increase in size of the
muscle belly and an increase in T2 signal return. Following
contrast media, the left lateral rectus shows evidence of
enhancement throughout the muscle belly.
Orbital myositis represents a subgroup of the ‘orbital pseudotumour syndrome’, which defines inflammation within any
structure in the confines of the orbit.17 It can involve a single
muscle or the entire orbital musculature and can be acute or
recurrent and chronic. It is most often described as idiopathic,
but has been associated with a number of systemic inflammatory
diseases.14,18 Diagnosis is based upon typical clinical presentation and radiological appearances on contrast-enhanced MRI.19
Biopsy is only indicated for an atypical presentation, rapid
progression of neurological deficit or if there is evidence of a
localised orbital mass.20
The mainstay of treatment is high dose corticosteroids
(prednisolone up to 100 mg/day, tapered accordingly) and
the response is typically rapid; pain resolving within 24 h.19
Chronic and recurrent disease may be attributed to delays in
diagnosis, treatment or insufficient doses of steroid.
Recurrences can be bilateral, extend beyond the orbital
musculature and may lead to diffuse systemic muscle
inflammation.21 In aggressive disease, pulsed intravenous
Recurrent posterior scleritis and orbital myositis as extra-intestinal manifestations of Crohn's disease: Case report and
systematic literature review
341
methylprednisolone can be effective.20 In steroid-refractory
cases, immunomodulators including methotrexate and
ciclosporin, cytotoxic agents such as cyclophosphamide,
anti-TNF therapy, and radiotherapy have been tried with
variable benefit.20,22
There is significant relapse risk reported with most
modalities of treatment for recurrent orbital myositis.22
Cyclophosphamide has been used for refractory orbital
pseudotumours, with the advantages of avoiding long-term
steroid therapy and the malignant potential of radiation
treatment.24,25 Leone and Lloyd, based on their experience
of 45 patients with orbital inflammatory disease, found that
the two most refractory cases responded to oral cyclophosphamide (200 mg/day for 15–18 months) as adjunctive
therapy to prednisolone (up to 80 mg/day for 18 months),
establishing control of orbital inflammation at one year off
all medication.24 Paris et al., found that high dose
prednisolone (100 mg/day) plus intravenous pulsed cyclophosphamide (100 mg/day, five-day pulses, two cycles at
three-week intervals) given to five patients with orbital
pseudotumour refractory to steroids and radiotherapy,
caused remission of symptoms maintained for up to
11 years.25 Nevertheless, the decision to initiate cytotoxic
therapy should be made by experienced specialists, taking
account of the severity and refractory nature of the
inflammatory process, the potential for visual compromise
and response to other therapy.
Evidence for the use of cyclophosphamide in CD is limited.
There are isolated case reports 26 and small prospective
uncontrolled trials evaluating safety and efficacy 27–29 of
intravenous cyclophosphamide in steroid-refractory luminal
CD. There is no current evidence for use in fistulating CD.
The largest of these trials (16 patients),27 reported an 81%
(13/16 patients) remission in symptomatic disease (defined
by reduction in the CD activity index) within 8 weeks after 2
pulses of cyclophosphamide and maintenance with
azathioprine or methotrexate. This response was sustained
for a median of 19 months (range 1–45). The non-responders
had a longer duration of disease (mean 16 years), more
intense pre-treatment with immunosuppressives and a larger
number of prior surgical interventions. Over one-third of
patients (38%, 6/16 patients) experienced infectious side
effects; urinary tract infection, Candida spp. oesophagitis,
neutropenic sepsis, central venous catheter infection complicated by pneumonia. There were no deaths. Cyclophosphamide is not currently recommended for use in
inflammatory bowel disease.
Orbital myositis has been associated with other inflammatory conditions of the eye, such as uveitis and scleritis.23
The clinical presentation of posterior scleritis and orbital
myositis are similar, but important to differentiate, as orbital
myositis may be associated with increased risk of ocular
complications and requires more intensive treatment.14,19
This was illustrated in a retrospective case series of 103
patients (76 with scleritis, 27 with episcleritis) managed at
an ophthalmology centre.14 Eleven patients had evidence of
both orbital myositis and scleritis, with involvement of the
posterior sclera. Ocular complications such as cataract,
keratitis, uveitis, high intraocular pressure and glaucoma
occurred in two thirds (64%) of those with both myositis and
scleritis compared to a third (30%) with scleritis alone. Loss
of visual acuity at presentation affected a quarter (27%) of
patients with myositis and scleritis and persisted despite
treatment. Loss of visual acuity resolved with treatment in
three quarters (77%) of those without myositis.14
The coexistence of scleritis, orbital myositis and CD is
exceptional, and has been reported in just two patients. In
the retrospective case series detailed above,14 one patient
was reported to have scleritis, orbital myositis and CD (there
were no further details about this patient). In a retrospective
observational series of seven patients reporting the response
of refractory orbital myositis to infliximab,13 there were two
patients with CD, one with scleritis and orbital myositis. This
patient received treatment in the form of oral corticosteroids, retrobulbar triamcinolone injections, radiotherapy and
methotrexate, before scheduled infliximab every two
months relieved symptoms with no evidence of recurrence
at 27-month follow-up.13
This third reported case of posterior scleritis, orbital
myositis and CD establishes a sufficient pattern for it to be
considered an exceptional ocular extra-intestinal manifestation of CD. This combination occurs in female patients with
colonic CD, activity-associated extra-intestinal manifestations
(such as large joint arthropathy and pyoderma) and is
refractory to standard therapy. The pattern, once recognised,
should prompt early specialist referral so that biological or
cytotoxic therapy can be considered at an early stage in the
hope that the course of the disease can be modified.
Acknowledgements
EC was responsible for writing the draft manuscript, the
literature search, and collection and preparation of images
and tables. JFS was responsible for critical revision and
editing the manuscript. PF was responsible for editing the
manuscript. SPLT was responsible for obtaining patient
consent, critical revision and editing the manuscript. All
authors read and approved the final manuscript. SPLT is also
the guarantor of the article.
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