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Granulomatosis with polyangiitis provoked by trauma

Published:April 26, 2016DOI:https://doi.org/10.1016/j.jcjo.2016.02.011
      A 31-year-old Somali male bus driver presented with left periorbital swelling and diplopia after an alleged assault, having received punches to his face. Testing of ocular movements demonstrated restriction of left upgaze. Examination was consistent with an orbital floor fracture. Surgical exploration confirmed a fracture over the infraorbital nerve canal associated with soft tissue tethering and inferior rectus muscle entrapment. Surgical repair was successful.
      At a postoperative follow-up appointment, he had persistent eyelid swelling and conjunctival injection. Despite partial response to a short course of oral steroids, he developed progressive swelling, pain, and diplopia. Hypoglobus and proptosis (Fig. 1A) suggested a superior orbital mass.
      Fig. 1
      Fig. 1(A) Left-eye hypoglobus, proptosis, and upper lid swelling. (B) Postoperative computed tomography (CT) of orbits showing a superomedial orbital mass. (C) Retrospective analysis of CT of orbits at presentation showed a small superomedial orbital mass.
      A further computed tomography (CT) of the orbits revealed a superiomedial orbital mass (Fig. 1B) causing inferior globe displacement. A retrospective review of CT images at the time of presentation (Fig. 1C) revealed the same mass to be present, albeit smaller. Biopsies were taken of a firm rubbery mass in the superior orbit. These characteristics suggested an inflammatory origin. An autoimmune screen, including anti-nuclear antibodies (ANA), immunoglobulins, complement and anti-neutrophil cytoplasmic antibodies (ANCA) returned negative. Further tests showed normal renal function, urine dipstick, serum angiotensin converting enzyme (ACE), thyroid stimulating hormone (TSH), chest radiograph, and CT of the chest, abdomen, and pelvis. Histopathology showed a leukocytoclastic vasculitis, with tissue necrosis and established fibrosis, in keeping with small-vessel vasculitis and a diagnosis of GPA. GPA was confined to his orbit with no symptoms of nasal crusting, blockade, discharge, or hearing loss, and systematic enquiry was unremarkable.
      In addition to background high-dose oral prednisolone (1 mg/kg), he was given 2 infusions of cyclophosphamide 15 mg/kg, rituximab 1 g, and methylprednisolone 100 mg 2 weeks apart. By choosing rituximab here, cumulative exposure to cyclophosphamide was minimized, thereby reducing risk of subfertility. After a good response to this regime, oral methotrexate 15 mg weekly was commenced and prednisolone was tapered. After 6 months’ treatment, he was in remission, with complete resolution of hypoglobus, proptosis, and normal vision.
      In this case, when the patient’s past photographs were reviewed, hypoglobus was evident 12 months before the assault, and retrospective analysis of the CT scan at presentation showed the presence of an orbital mass. Both observations support the existence of GPA before presentation, and subsequent trauma appears to have provoked increased inflammatory activity and rapid growth of the orbital mass. To the best of our knowledge, this is the first reported case of trauma affecting activity of ocular GPA.
      Trauma has been shown to precipitate inflammatory disease previously, such as pyoderma gangrenosum occurring after knee trauma
      • Steenbrugge F.
      • Raaijmaakers M.
      • Caekebeke P.
      • et al.
      Pyoderma gangrenosum following trauma of the knee: a case of pathergy and review of orthopaedic cases.
      and necrotising scleritis at the site of previous ocular surgery.
      • O’Donoghue E.
      • Lightman S.
      • Tuft S.
      • et al.
      Surgically induced necrotising sclerokeratitis (SINS)–precipitating factors and response to treatment.
      We believe that our case also demonstrates trauma as an inflammatory stimulus, with potential to change the course of disease in ocular GPA.
      In GPA, orbital involvement ranges from approximately 31% to 61%
      • Stone J.H.
      Wegener’s Granulomatosis Etanercept Trial Research Group. Limited versus severe Wegener’s granulomatosis: baseline data on patients in the Wegener’s granulomatosis etanercept trial.
      and can occur at presentation as well as in established disease,
      • Holle J.U.
      • Voight C.
      • Both M.
      • et al.
      Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage.
      with 7%–45% developing orbital pseudotumour, which accounts for 22% of eye manifestations of GPA.
      • Haynes B.F.
      • Fishman M.L.
      • Fauci A.S.
      • et al.
      The ocular manifestations of Wegener’s granulomatosis. Fifteen years experience and review of the literature.
      The most common eye manifestation, however, is scleritis, which accounts for up to 50% of ocular GPA.
      • Holle J.U.
      • Voight C.
      • Both M.
      • et al.
      Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage.
      Furthermore, there are a constellation of other manifestations, including conjunctivitis, episcleritis, keratitis, uveitis, retinal disease and nasolacrimal disease.
      • Holle J.U.
      • Voight C.
      • Both M.
      • et al.
      Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage.
      It is postulated that orbital masses arise from paranasal sinuses and perforate the orbit by erosion and infiltration through bone. This is supported by high frequency of concomitant sinus involvement and detection of bony perforations on imaging.
      • Stone J.H.
      Wegener’s Granulomatosis Etanercept Trial Research Group. Limited versus severe Wegener’s granulomatosis: baseline data on patients in the Wegener’s granulomatosis etanercept trial.
      • Provenzale J.M.
      • Mukherji S.
      • Allen N.B.
      • Castillo M.
      • Weber A.W.
      Orbital involvement by Wegener’s granulomatosis: imaging findings.
      As a mass enlarges in the orbit, there is risk to sight by direct compression of the optic nerve and proptosis, exposing the cornea to exposure keratopathy.
      • Holle J.U.
      • Voight C.
      • Both M.
      • et al.
      Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage.
      Common symptoms include visual loss, eye pain, proptosis, and progressive diplopia because of extraocular muscle dysfunction. It is essential to seek symptoms of epistaxis, nasal blockage and crusting suggestive of GPA in assessment of patients with suspected orbital mass, along with careful examination of the nasal mucosa and review of the paranasal sinuses on imaging.
      Treatment of orbital masses with rituximab has been demonstrated to be effective in inducing clinical remission in inflammatory eye disease refractory to conventional immunosuppression.
      • Taylor S.R.
      • Salama A.D.
      • Joshi L.
      • et al.
      Rituximab is effective in the treatment of refractory ophthalmic Wegener’s granulomatosis.
      • Suhler E.B.
      • Lim L.L.
      • Beardsley R.M.
      • et al.
      Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial.
      This supports the finding of rituximab noninferiority to cyclophosphamide in management of systemic ANCA-positive vasculitis in a large randomized controlled trial, which included 151 patients with GPA.
      • Stone J.H.
      • Merkel P.A.
      • Spiera R.
      • et al.
      Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
      This case also demonstrates the benefit of an early aggressive immunosuppressive strategy, achieving early remission and avoiding harm of ongoing, smouldering inflammation, which risks permanent visual loss.

      References

        • Steenbrugge F.
        • Raaijmaakers M.
        • Caekebeke P.
        • et al.
        Pyoderma gangrenosum following trauma of the knee: a case of pathergy and review of orthopaedic cases.
        Injury. 2011; 42: 421-423
        • O’Donoghue E.
        • Lightman S.
        • Tuft S.
        • et al.
        Surgically induced necrotising sclerokeratitis (SINS)–precipitating factors and response to treatment.
        Br J Ophthalmol. 1992; 76: 17-21
        • Stone J.H.
        Wegener’s Granulomatosis Etanercept Trial Research Group. Limited versus severe Wegener’s granulomatosis: baseline data on patients in the Wegener’s granulomatosis etanercept trial.
        Arthritis Rheum. 2003; 48: 2299-2309
        • Holle J.U.
        • Voight C.
        • Both M.
        • et al.
        Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage.
        Rheumatology. 2013; 52: 875-882
        • Haynes B.F.
        • Fishman M.L.
        • Fauci A.S.
        • et al.
        The ocular manifestations of Wegener’s granulomatosis. Fifteen years experience and review of the literature.
        Am J Med. 1977; 63: 131-141
        • Provenzale J.M.
        • Mukherji S.
        • Allen N.B.
        • Castillo M.
        • Weber A.W.
        Orbital involvement by Wegener’s granulomatosis: imaging findings.
        Am J Roentgenol. 1996; 166: 929-934
        • Taylor S.R.
        • Salama A.D.
        • Joshi L.
        • et al.
        Rituximab is effective in the treatment of refractory ophthalmic Wegener’s granulomatosis.
        Arthritis Rheum. 2009; 60: 1540-1547
        • Suhler E.B.
        • Lim L.L.
        • Beardsley R.M.
        • et al.
        Rituximab therapy for refractory orbital inflammation: results of a phase 1/2, dose-ranging, randomized clinical trial.
        JAMA Ophthalmol. 2014; 132: 572-578
        • Stone J.H.
        • Merkel P.A.
        • Spiera R.
        • et al.
        Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
        N Engl J Med. 2010; 363: 221-232