Annals of B Pod: Sarcoidosis Optic Neuropathy

HISTORY OF PRESENT ILLNESS

A female in her 60s with a past medical history of hypothyroidism and celiac disease presents with progressive vision loss in her left eye. She was initially evaluated by an ophthalmologist for no light perception in the left eye and referred to the emergency department for further testing and imaging. The patient noticed that her left eye was more swollen compared to the right. She went to bed and woke up in the middle of the night with significant pain in her left eye, floaters in her vision, and “kaleidoscope vision.” Upon waking up, she was unable to see light or hand waving. She has had similar episodes of eye pain in the past with swelling around her eye, but these episodes resolved spontaneously. She denies any trauma to her eye, chemical injury, or drainage. She does not have any pain or vision loss in her right eye. Eight months prior the patient had a CT scan of the neck to evaluate a vocal cord polyp, which revealed bilateral diffuse extraocular muscle enlargement with effacement of fat planes at the bilateral orbital apices, consistent with thyroid eye disease or IgG4 related ophthalmic disease. She was seen by ophthalmology at that time, had a normal eye exam, and no intervention other than periodic monitoring was recommended.

PAST MEDICAL HISTORY: Celiac disease, hypothyroidism

PAST SURGICAL HISTORY: Tonsillectomy, vocal cord polyp removal

MEDICATIONS: levothyroxine

ALLERGIES: Penicillin, sulfonamide antibiotics

NOTABLE DIAGNOSTICS

ESR 6 mm/hr (0-30 mm/hr)

CRP 6.8 mg/L (1.0-10.0 mg/L)

T4 1.04 ng/dL (0.61-1.76 ng/dL)

TSH 1.78 uIU/mL (0.45-4.12 uIU/mL)

CT Orbits with Contrast: Diffuse, bilateral enlargement of extraocular muscles with effacement of the fat planes at the orbital apices that is concerning for optic nerve compression. Bony remodeling of orbital walls related to chronic pressure erosion. Bilateral mild exophthalmos increased on left compared to previous CT imaging study from 8 months prior.

PHYSICAL EXAM

Vitals: T 97.7F HR 76 BP 120/94 RR 18 SpO2 99% RA

The patient is in no acute distress. Examination of the left eye reveals proptosis. Upon direct light exposure, there is no left pupillary constriction. There is left pupillary construction upon indirect light exposure, and there is normal right pupillary constriction upon direct and indirect light exposure. Upon testing of extraocular movements, the patient is able to look medially with the left eye but is unable to move her left eye laterally or upward. Extraocular movements are intact in the right eye. Visual acuity testing reveals no light perception in the left eye, and 20/50 vision in the right eye. Intraocular pressures are 17 in the left eye and 13 in the right eye. The remainder of the patient’s physical exam is unremarkable.

HOSPITAL COURSE

Ophthalmology evaluated the patient in the emergency department and performed a dilated slit lamp exam, finding left optic disc edema. She was admitted to the Medicine service with a diagnosis of compressive optic neuropathy of the left eye and bilateral thyroid eye disease. Otolaryngology was consulted for surgical decompression of the bilateral orbits, which occurred without complication. Serial ophthalmologic examinations revealed that the patient had no improvement in light perception in her left eye and developed visual hallucinations in the left eye. She also started to see gray spots in her right eye and had worsening tunnel vision in her right eye. Further lab workup including anti-TPO antibodies were negative, inconsistent with the diagnosis of thyroid eye disease. Biopsies obtained during surgery showed granulomas of the left nasal contents, left medial rectus muscle, and right periorbital area. None of the cultures of the tissue grew any organisms. The rheumatology team was consulted at this time and thought that the patient’s presentation was more consistent with a diagnosis of ocular sarcoidosis given her biopsy results and negative anti-TPO antibodies. They recommended that the patient be started on an aggressive sarcoidosis regimen including infliximab, methotrexate, and continued steroids to preserve vision in her right eye. Further sarcoidosis workup including imaging indicated that the patient’s disease was limited to ocular sarcoidosis. At discharge, the patient still had no light perception in her left eye, but normal vision in her right eye.

DISCUSSION

Pathophysiology

Sarcoidosis is a granulomatous disease that can affect virtually every organ system in the body but is found commonly in the lungs and lymph nodes. In sarcoidosis, non-caseating granulomas accumulate in body tissues, often resulting in chronic systemic inflammation and fibrosis. Granulomas are composed of macro-phages, epithelioid cells, and lymphocytes and form in order to contain a pathogen and protect surrounding tissue. As they mature, granulomas may become surrounded by collagen and fibroblasts, leading to sclerosis. The inciting factor causing granuloma formation in sarcoidosis is unknown, but many studies have found associations with environmental exposures such as wood-burning stoves, tree pollen, inorganic particles, insecticides, and mold. In addition, bacterial DNA and RNA has been found in the granulomatous tissue of sarcoidosis. There have also been occupational studies that have shown association with the US Navy, metalworking, firefighting, and the handling of building supplies. Genetic studies have found an increased incidence in the disease among those who have a family member with sarcoidosis, and there are several genes proposed to convey susceptibility to sarcoidosis. [1]

Epidemiology

The prevalence of sarcoidosis is variable depending on the demographic of the population. In the United States, an annual incidence of 35.5 per 100,000 black patients and 10.9 per 100,000 white patients is estimated, with black females as the most commonly affected population. Patients are usually under the age of 50 when diagnosed, but can be seen very rarely seen in children. [2,3] The prognosis and clinical course of sarcoidosis is highly variable, with spontaneous remission in about two-thirds of cases and 10-30% of cases becoming chronic or progressive.

Figure 1: Chest x-ray showing hilar lymphadenopathy, which is characteristic of pulmonary sarcoidosis

Clinical Presentation

Sarcoidosis has a wide variety of presentations in the emergency department. Patients may even be asymptomatic and present with incidental findings characteristic of the disease, such as chest radiography with bilateral hilar lymphadenopathy (figure 1). [1] Patients may have non-specific constitutional symptoms, such as fever, malaise, fatigue, and weight loss. [5] The most common organ system involved is the lungs, which are involved in about 90% of cases, and thus respiratory symptoms are the most common presentation of the disease. [5] Of particular note to the emergency physician, 11% of sarcoidosis patients have hypercalcemia, which is thought to be due to calcitriol secreted by the granulomas, leading to increased absorption of calcium in the intestines. [2,5] Various clinical presentations of sarcoidosis are summarized in table 1.

Ocular involvement has been reported in 15-25% of cases of sarcoidosis and can be isolated or may be the initial presenting symptom. Most commonly it affects both eyes, and it can involve all parts of the eye and surrounding tissues. [5] The most common presentation of ocular sarcoidosis is granulomatous uveitis, whereas optic neuropathy secondary to sarcoidosis, as was seen in this patient, is much less common. Granulomatous lesions of the surrounding tissues, leading to compression of the optic nerve, or granulomatous infiltration of the optic nerve itself, can cause optic neuropathy leading to painless or painful vision loss or changes in color perception. [6,7]

Table 1. Various clinical presentations of sarcoidosis [5]

Diagnosis & Workup

While we may suspect the disease in the emergency department, we will not make the final diagnosis of sarcoidosis, and consultation of rheumatology is of paramount importance. The diagnosis of sarcoidosis is made when there is a compatible clinical picture and a biopsy showing non-caseating epithelioid granulomas, as well as exclusion of other possible causes of granulomas, such as infection and foreign bodies. [8] Testing in the emergency department is usually directed by the presenting symptoms and organ system involved, but a calcium should always be checked if the diagnosis of sarcoidosis is suspected. [5]

Treatment

Treatment of sarcoidosis is not always necessary since most patients are not disabled by the illness. If organ function is threatened, treatment is initiated. Absolute indications for treatment include neurologic, cardiac, or ocular involvement, and hypercalcemia. Corticosteroids are the mainstay of treatment, but immunomodulating drugs such as hydroxychloroquine, methotrexate, azathioprine, and cyclophosphamide have been used as well.

SUMMARY

Sarcoidosis is a disease characterized by the accumulation of granulomas in any body tissue, but most commonly the lungs. Sarcoidosis patients can present with a wide variety of complaints, including vision loss due to optic neuropathy, as was seen in this patient. Ultimately the diagnosis is made by biopsy of granulomatous tissue, and while treatment may not always be necessary, the mainstay of treatment is corticosteroids.

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AUTHORED BY CALYN CRAWFORD, MD

Dr. Crawford is a PGY-3 in Emergency Medicine at the University of Cincinnati

EDITING BY THE ANNALS OF B POD EDITORS

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REFERENCES

1. Thomas KW, Hunninghake GW. Clinical Presentation and Diagnostic Evaluation. JAMA. 2003 Jun 25;289:3300-3.

2. Iannuzzi MC, Rybicki BA, Teirstein AS. Medical progress. Sarcoidosis. N Eng J Med. 2007;357:2153-65.

3. Dempsey OJ, Paterson EW, Kerr KM, Denison AR. Sarcoidosis BMJ. 2009; 339: b3206. Doi: https://doi. org/10.1136/bmj. b3206.

4. Costabel U, Hunninghake GW. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis statement committee. American thoracic society. European respiratory society. World association for sarcoidosis and other granulomatous disorders. European Respiratory Journal. 1999 Oct 1;14(4):735-7.

5. Pollack Jr CV, Jorden RC. Recognition and management of sarcoidosis in the emergency department. The Journal of emergency medicine. 1993 May 1;11(3):297-308.

6. Pula JH, MacDonald CJ. Current options for the treatment of optic neuritis. Clinical Ophthalmology (Auckland, NZ). 2012;6:1211.

7. Lally E, Murchison AP, Moster ML, Bilyk JR. Compressive optic neuropathy from neurosarcoidosis. Ophthalmic Plastic & Reconstructive Surgery. 2015 May 1;31(3):e79.

8. Heinle R, Chang C. Diagnostic criteria for sarcoidosis. Autoimmunity reviews. 2014 Apr 1;13(4-5):383-7.

9. Ungprasert P, Ryu JH, Matteson EL. Clinical manifestations, diagnosis, and treatment of sarcoidosis. Mayo Clinic Proceedings: Innovations, Quality & Outcomes. 2019 Sep 1;3(3):358-75.