Orbital Inflammatory Disease: Unusual Presentation of Enthesitis in an HLA-B27 Spondyloarthropathy

Abstract

Background: Orbital inflammatory disease can complicate many systemic inflammatory disorders, including sarcoidosis, vasculitis, Crohn’s disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis and scleroderma, but has not been reported with spondyloarthropathies.

Observations: The authors describe a 29-year-old woman who developed orbital myositis, in addition to anterior uveitis, sacroiliitis and peripheral arthritis, as a complication of an underlying HLA-B27 related spondyloarthropathy, which responded temporarily to corticosteroid therapy and more completely to adalimumab.

Conclusions: The patient reported herein presents with orbital inflammation as an extra-articular manifestation of HLA-B27 associated undifferentiated spondyloarthropathy. We propose that enthesitis is the likely mechanism of orbital inflammation in this patient.

KEYWORDS::

• Orbital inflammatory disease
• Orbital myositis
• Spondyloarthropathy
• Enthesitis
• HLA-B27
• Adalimumab

Orbital inflammatory disease (OID) consists of several disorders that manifest as inflammatory involvement of some or all of the structures of the orbit external to the ocular globe. In addition to Graves ophthalmopathy, several systemic inflammatory disorders, including sarcoidosis and Wegener granulomatosis, are well known to affect the orbital tissues.^1,2 Additionally, localized conditions, such as idiopathic orbital inflammation (popularly known as orbital pseudotumor) or infectious (orbital cellulitis) or malignant processes (ocular lymphoma), may present in similar fashion.¹ Among the systemic inflammatory diseases associated with OID are several other immunologic disorders, including Crohn disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, and scleroderma.² However, we are unaware of an association between OID and HLA-B27-related conditions (e.g., ankylosing spondylitis, reactive arthritis) in the English-language literature. We report a patient with orbital inflammation as an extra-articular manifestation of an HLA-B27-associated spondyloarthropathy.

CASE PRESENTATION

A 29-year-old Anglo-Celtic woman originally noted bilateral knee pain and swelling at age 7, which recurred for several years. At age 17, she developed synovitis of the ankles, dactylitis involving several digits on each foot, and elbow and shoulder arthralgias. Her symptoms responded to nonsteroidal anti-inflammatory therapy, but use of these agents was limited by hematochezia. Evaluation for the presence of inflammatory bowel disease, including colonoscopy and small bowel radiographic examination, was negative. Her symptoms abated after several months. At age 21, she developed photophobia, visual blurring, and diplopia. Although her photophobia improved with the use of topical corticosteroid ophthalmic drops, she required systemic prednisone treatment for 2 months to fully control her ocular inflammation. At age 22, she noted ankle synovitis, left hip pain, anterior chest wall pain, neck and low back pain, with 2 h of morning stiffness. She again developed photophobia, conjunctival injection, and proptosis of her right eye, consistent with recurrent orbital pseudotumor, which again responded to oral prednisone. There was no history of dysuria or mucocutaneous lesions or prior evidence of psoriasis, syphilis, sarcoidosis, or tuberculosis.

Physical examination was notable for the absence of rash, subcutaneous nodules, oral or nasal mucosal lesions, lymphadenopathy, or visceromegaly. Musculoskeletal examination revealed tenderness overlying the left sacroiliac joint; positive Patrick’s sign and Gaenslen’s maneuver on the left; negative Schober’s maneuver, with normal spinal range of motion; no peripheral synovitis. Ocular examination revealed palpebral conjunctival inflammation, ciliary flush, and periorbital swelling of the right eye on examination, without evidence of scleritis or posterior uveitis on fundoscopic examination, consistent with recurrent bilateral anterior uveitis and unilateral inflammatory orbital pseudotumor.

Laboratory data were notable for ESR (Westergren) 107 mm/h, hemoglobin 11.9 g/dL, with normal leukocytes and platelets. HLA-B27 determination was positive; rheumatoid factor and anti-nuclear antibody testing were negative. Immunoglobulin electrophoresis showed a polyclonal pattern, with total IgG elevated at 1458 mg/dL (normal, 614–1295 mg/dL), but individual immunoglobulin class and IgG subclass determinations were within normal range. X-ray of the pelvis revealed sclerosis of the left sacroiliac joint with erosive changes noted in the symphysis pubis. Chest x-ray, tuberculin test, and serologic testing for ACE, ANCA, Lyme disease, Chlamydia, and syphilis were negative or normal. Computed tomography of the orbits revealed no obvious uveoscleral thickening, lacrimal gland enlargement, or retrobulbar masses; the optic nerves appeared normal; the left medial rectus muscle appeared distended, with swelling noted of its tendinous insertion, conferring a fusiform configuration. The patient’s insurance carrier refused magnetic resonance imaging. No retrobulbar biopsy was attempted.

A diagnosis of an HLA-B27-associated undifferentiated spondyloarthropathy presenting primarily with sacroiliitis and oligoarthritis was made. Because of the more peripheral distribution of her articular involvement, the intolerance of NSAIDs, and the presumed extra-articular manifestation (inflammatory orbital pseudotumor), treatment with enteric-coated sulfasalazine 2000 mg daily in divided doses was initiated. On this regimen, resolution of her ankle and knee swelling and inflammatory ocular findings was achieved. Prednisone was tapered and discontinued over the next 2 months and she was maintained on sulfasalazine alone for 1 year. She continued to note mild neck, anterior chest wall, and low back pain, but had no restricted mobility.

At the patient’s request, sulfasalazine was discontinued in advance of intended pregnancy and she remained well for the next 2 years. Nine months postpartum, at age 25, she developed recurrent left knee synovitis, neck and low back pain, intense conjunctival injection, and proptosis of her right eye, consistent with recurrent orbital pseudotumor, which again required oral prednisone. Sulfasalazine was restarted and she promptly developed a diffuse morbiliform eruption, which resolved within 2 weeks of discontinuation. The drug-induced dermatitis recurred despite sulfasalazine hyposensitization. She required daily prednisone at doses >20 mg to control her periorbital inflammation, although her ankle synovitis had resolved. Repeat tuberculin skin testing, chest radiography, and serologies for syphilis, Lyme disease, and ACE were normal. She was then treated with adalimumab 40 mg subcutaneously. After 2 weekly doses, resolution of her periorbital swelling occurred, as did her residual chest wall, neck, and back pain. Her prednisone dose was tapered and discontinued during the following 6 weeks. After 6 months of therapy, her dose of adalimumab was decreased to 40 mg every other week. She has remained symptom-free for the past 4 years.

DISCUSSION

Orbital inflammation, in general, encompasses inflammatory conditions that affect some or all of the structures contained within the orbit external to the ocular globe. The inflammatory process may be diffuse in nature with involvement of several orbital structures or localized to a single orbital structure, such as the lacrimal gland, extraocular muscles, and orbital fat.² Therefore, the nature of involvement of orbital structures, determined by the clinical and radiological features and, possibly, tissue biopsy, may help distinguish some of the causes of orbital inflammation.

Our patient presented with recurrent orbital pain, diplopia, periorbital edema, and proptosis, in conjunction with sacroiliitis and peripheral arthritis. Although thyroid-associated ophthalmopathy is the most common cause of orbital inflammation in adults,³ our patient did not have any clinical and laboratory features suggesting thyroid disease. Similarly, there was no evidence to suggest underlying lymphoproliferative disease, the next most common cause of orbital inflammation. Although orbital inflammation has been described in association with isolated retroperitoneal fibrosis, multifocal fibrosclerosis (retroperitoneal and mediastinal fibrosis, Riedel thyroiditis) and IgG4-related sclerosing diseases,⁴ our patient did not have any features of these diseases. Similarly, a detailed history, physical exam, and laboratory evaluation helped to exclude other causes of orbital inflammation in our patient, including sarcoidosis, Wegener granulomatosis, Crohn disease, rheumatoid arthritis, systemic lupus erythematosus, and infection. Without confirmatory evidence of other causes of orbital inflammation, a diagnosis of HLA-B27-associated undifferentiated spondyloarthropathy with orbital inflammation was made. It remains possible that a limited presentation of a systemic inflammatory disease, such as Crohn disease, may not have been recognized.

Among the ocular manifestations of HLA-B27-related diseases, acute anterior uveitis is one of the most commonly described. However, we are unaware of any descriptions of an association between HLA-B27-related diseases and involvement of tissues external to the ocular globe. A case of psoriatic arthritis with OID has been noted, but this patient had no evidence of spinal involvement and was HLA-B27 negative.⁵

Many of the manifestations of spondyloarthropathies and the peculiar disease distribution at several extraskeletal sites, e.g., heart and lungs, remain difficult to explain. Many of these sites of disease involvement share certain common anatomical, biomechanical, and even pathological features, including the widespread distribution of fibrocartilage. Enthesitis arises at these fibrocartilagenous sites, presumably as a consequence of high shear and compression forces, resultant microtrauma, aberrant tissue repair mechanisms, and possibly bacterial sensitization and molecular mimickry.⁶ Based on the finding of inflammation and swelling of the tendinous insertion of the extraocular muscle on orbital imaging in our patient, we propose that this presentation may represent an atypical location of enthesitis.

Although rare, HLA-B27-related spondyloarthropathies should be included in the differential diagnosis of orbital inflammatory disease.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.