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Acute orbital sarcoidosis with preceding fever and erythema nodosum

      A 53-year-old previously healthy Caucasian male presented to an emergency department with fever, well-circumscribed tender erythematous nodules of the shins, bilateral plantar pain, and bilateral ankle swelling and pain of 1-week duration. He was discharged without a diagnosis and his symptoms began to spontaneously resolve over the next 3 days. A month later, he developed new diplopia, left lower eyelid swelling, and a palpable orbital lump.
      These new ocular findings prompted a referral to our ophthalmology clinic for further assessment. On examination, best-corrected visual acuities were 20/20, colour plates were full bilaterally, and there was no relative afferent pupillary defect. The left lower eyelid appeared full and an inferior orbital mass was palpable just posterior to the orbital rim with associated increased firmness on retropulsion. The left eye demonstrated limitation of depression in attempted down gaze. There was no proptosis with exophthalmometry or axial displacement of the globe. Findings of the remainder of the eye examination were normal.
      Computed tomography of the head revealed a homogenous mass located in the inferior orbit of the left eye. The mass was continuous with the muscle tendons of the inferior oblique and inferior rectus muscles, displacing the globe slightly upward. There were no radiographic signs of bone or globe invasion.
      During an orbital biopsy and surgical debulking procedure, the mass was found to encompass the inferior oblique muscle with adherence to the inferior rectus. Pathologic examination demonstrated extensive noncaseating granulomatous inflammation with negative stains for fungal, acid fast, and bacterial organisms, and was therefore felt to be consistent with sarcoidosis. Figure 1 shows the clinical appearance of the patient, imaging, and histology of the biopsy specimen.
      Fig. 1
      Fig. 1(A) Clinical appearance of the patient, in upgaze, at time of presentation to our oculoplastic clinic. (B) Computed tomography imaging showing inferior orbital mass involving the rectus muscle. (C) Low-power (50×) and (D) high-power (400×) view of surgically obtained orbital specimen demonstrating replacement of orbital fat by noncaseating granulomatous inflammation and a granuloma with multinucleated giant cells, respectively. All specimens were stained with hematoxylin phloxine and saffron stains.
      Blood work completed after the biopsy results yielded a mildly elevated angiotensin converting enzyme level (68 U/L) and C-reactive protein (3.4 mg/L) but normal liver function tests, calcium, and inflammatory markers. Findings of chest x-ray and pulmonary function tests were normal. A diagnosis of Lofgren’s syndrome was made based on the constellation of acute onset arthritis, rash consistent with erythema nodosum, fever, and new extrapulmonary sarcoid mass.
      After the orbital debulking procedure, the patient’s ocular symptoms resolved with the exception of very mild diplopia in far upgaze. Repeat imaging demonstrated a residual mass at the surgical site that was felt to represent scar tissue but persistent disease is a possibility. Given his lack of symptoms, no treatment has been initiated to date. His clinical course has remained stable for the last 11 months and he continues to be followed closely for any sign of disease progression.

      Discussion

      Ocular and ocular adnexal involvement with sarcoidosis is well known and estimated to affect 25%–60% of people with the disease.
      • Rothova A.
      Ocular involvement in sarcoidosis.
      Of the ocular adnexal structures, the lacrimal gland is the most likely to be affected.
      • Rothova A.
      Ocular involvement in sarcoidosis.
      Löfgren syndrome is an acute form of sarcoidosis, characterized by the triad of erythema nodosum and/or inflammatory ankle arthritis, bilateral hilar lymphadenopathy, and fever.
      • Kirresh O.
      • Schofield J.
      • George G.
      Acute sarcoidosis: Lofgren’s syndrome.
      A systematic review of the last 20 years identified only a single case of Löfgren syndrome with ocular adnexal involvement that was reported to affect the eyelid.
      • Hmaled W.
      • Baccouri R.
      • Zbiba W.
      • et al.
      Lofgren syndrome revealed by eyelid tumor.
      Löfgren syndrome is considered a distinct clinical entity affecting up to 20%–30% of Caucasians and 4% of Asian
      • Siltzbach L.E.
      • Jame D.G.
      • Neville E.
      • et al.
      Course and prognosis of sarcoidosis around the world.
      and Indian
      • Sharma S.K.
      • Soneja M.
      • Sharma A.
      • et al.
      Rare manifestations of sarcoidosis in modern era of new diagnostic tools.
      adults with sarcoidosis.
      Recognition of the classic symptom pattern is key to the diagnosis. The course of disease is characterized by a prompt and spontaneous resolution of symptoms (erythema nodosum and fever) within approximately 6 weeks to 6 months. Steroids are rarely required in the treatment of this syndrome, and nonsteroidal anti-inflammatory drugs (NSAIDs) are often used if symptomatic relief is necessary. Some experts reason that pathologic confirmation of disease is unnecessary if all clinical diagnostic criteria are met and the symptom resolution proceeds as expected.
      American Thoracic Society: Medical Section of the American Lung Association
      Statement on sarcoidosis.
      Common extrapulmonary manifestations include anterior uveitis, lymphadenopathy, and skin granulomas.
      • Rothova A.
      Ocular involvement in sarcoidosis.
      Our patient presented with acute orbital sarcoidosis with preceding fever and erythema nodosum. The diagnostic criteria of Löfgren syndrome were not met in the case presented because we failed to detect hilar lymphadenopathy on chest x-ray. Of note, the x-ray was completed several months after onset of initial presentation of symptoms. For a large portion of patients, the resolution of lymphadenopathy occurs within 1 year
      • Lynch III, J.P.
      • Kaerooni E.M.
      • Gay S.E.
      Pulmonary sarcoidosis.
      and up to 50% of patients with suspected sarcoidosis can have a negative chest x-ray but positive bronchoalveolar lavage.
      • Takada K.
      • Matsumoto S.
      • Kojima E.
      • et al.
      Diagnostic management of patients with suspected ocular sarcoidosis.
      Therefore, hilar lymphadenopathy may have initially been present and/or gone undetected for the case described here.
      Because of the acute onset of orbital symptoms and overlap in symptomatology with Löfgren syndrome, we elected to withhold steroid treatment and instead treat symptomatically.
      To our knowledge this is the first case of acute orbital sarcoidosis to manifest as part of a suspected acute sarcoidosis syndrome. Given the frequently benign course of Löfgren syndrome and lack of need for aggressive treatment, in contrast to other manifestations of ocular adnexal sarcoidosis, it is an important association for ophthalmologists to be aware of.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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