BLOG: Sarcoidosis diagnosis and treatment

I have always been interested in sarcoidosis in the way it presents and its diagnostic dilemma, so I would like to pose three test questions and follow up with a discussion to build upon the questions.

Question 1: The most frequent presenting complaint in orbital sarcoid is:

A. Swelling or a palpable mass

B. Proptosis/globe displacement

C. Dry eyes

D. Pain

E. Visual loss

The answer is A. The most frequent presenting complaint is swelling or a palpable mass. Proptosis/globe displacement or ptosis seems to be the second most common sign in recent case series. Dry eye symptoms including blurring, redness, pain and tearing may occur with lacrimal gland involvement, proptosis or other eyelid/cutaneous involvement. Significant pain from the granulomatous lesion itself, however, is not a common feature. Visual loss can occur with direct involvement of the optic nerve or dural sheath.

Question 2: Which test is the most valuable in diagnosing orbital sarcoid?

A. Serum ACE

B. Serum lysozyme

C. Galium scan

D. Direct orbital biopsy

E. Serum calcium

The answer is D. Laboratory studies in the setting of isolated orbital disease may be of limited value due to their low sensitivity. Elevation of serum ACE is inconsistent with the current literature on orbital and adnexal sarcoidosis. Direct orbital biopsy looking for a noncaseating granuloma may be confirmatory.

Question 3: The tissue most commonly involving in orbital sarcoid is:

A. Intraconal fat

B. Eyelid skin

C. Lacrimal gland

D. Extraocular muscles

E. Optic nerve dural sheath

The answer is C. Anterior uveitis is the most common ocular presentation in sarcoidosis. In addition, lacrimal gland involvement may occur from 7% to 15% of systemic sarcoid in general. When the orbit is known to be involved, the rate of lacrimal gland involvement may be increased to 55%.

As a multisystem disease, sarcoid affects the lungs most commonly, but involvement of the lymphatics, liver, central nervous system, skin and ocular tissues is quite common. While it can occur at any age, it typically presents between the third and fifth decades. Sarcoidosis occurs in all ethnic and racial groups, but it has its highest prevalence in African-Americans and Northern European whites and occurs more commonly in women than in men.

The etiology of sarcoid remains unclear. The pathologic lesion, however, is a noncaseating granuloma in the form of epithelioid cells and Langhans multinucleated giant cells. Ophthalmic involvement in sarcoidosis affects approximately 25% to 60% of the patients with this multisystem disease. By far the most common presentation of ocular sarcoidosis is anterior uveitis, with chorioretinitis, conjunctival granulomas and eyelid granulomas also being seen. Systemic orbital and adnexal manifestations in this disease, however, are relatively uncommon. The literature is limited to a number of case reports and a few case series. Of the extraocular orbital tissues affected, lacrimal gland infiltration is the most common. Involvement of the orbital soft tissue, extraocular muscles, lacrimal sac and optic nerve is also seen. In distinction to the systemic disease, orbital sarcoid is seen most commonly in the fifth to seventh decades with a median age of 50 to 55 years.

The onset of orbital and adnexal sarcoid may be chronic or subacute. The most frequent presenting complaint is a swelling or palpable mass. Proptosis/globe displacement or ptosis seems to be the second most common sign in recent case series. Dry eye symptoms, including blurriness, redness, pain and tearing, may occur with lacrimal gland involvement, proptosis or other eyelid/cutaneous involvement. Significant pain from the granulomatous lesion itself, however, is not a common feature. Visual loss can occur with direct involvement of the optic nerve or its dural sheath. Any diplopia may occur with extraocular muscle involvement. Cutaneous manifestations of the eyelid skin usually occur in the form of millet-seed nodules and sarcoid granulomas of the eyelid skin. Sarcoid involvement of the nasolacrimal drainage system is also uncommon. When it does occur, however, symptoms include recurrent epiphora despite dacryocystorhinostomy (DCR).

Soft tissue involvement of the orbit comes in two varieties, diffuse and discrete. Discrete lesions seem to involve the anterior/inferior orbit in more than half the cases. Diffuse orbital lesions are more common when there is active systemic disease. Extraocular muscle involvement is really isolated and is seen more often with the diffuse orbital form.

Following imaging of the orbits by CT or MRI, the definitive diagnosis of orbital or adnexal sarcoidosis requires histopathologic confirmation of noncaseating epithelioid granulomas by biopsy of the involved tissues. Special stains for fungi and microbacteria should be used to rule out infectious etiologies.

Some authors suggests that the term orbital sarcoid should not be used in the absence of systemic findings. If orbital or adnexal sarcoid is suspected as an initial presentation of the disease, it is obligatory for either the ophthalmologist or the primary care physician to initiate an extensive systemic workup. This includes chest X-ray and/or high-resolution CT to look for mediastinal lymphadenopathy, serum angiotensin-converting enzyme (ACE) levels, serum lysozyme levels, serum calcium levels, liver function tests, Galium scans, and tuberculin skin tests with anergy. Ninety percent of patients with sarcoid will have an abnormal chest X-ray or abnormal high-resolution CT, after which biopsy of the mediastinal lymph nodes will confirm the diagnosis.

Laboratory studies in the setting of isolated orbital disease may be of limited value due to their low sensitivity. Elevation of serum ACE is inconsistent with the current literature on orbital and adnexal sarcoid. The two most recent case series show an elevated ACE level in 20% to 62.5% of patients with orbital/adnexal disease. Another study from the division of ophthalmology at the Nippon Medical School in Japan demonstrated low sensitivity for serum ACE levels as well as serum lysozymes and Galium scans in diagnosing ocular sarcoid. In cases in which systemic disease is active, however, serum ACE levels may be elevated in 60% to 90% of patients. It should also be noted that an ACE level can also be nonspecific, as it may be elevated in tuberculosis, leprosy, silicosis, primary biliary cirrhosis, asbestosis and histoplasmosis.

As mentioned above, anterior uveitis is the most common presentation of sarcoidosis. In additional, lacrimal gland involvement may occur in various series from 7% to 15% of systemic sarcoidosis in general. When the orbit is known to be involved, the rate of lacrimal gland involvement may increase to 55%. Suspicion of sarcoidosis in an African-American patient with uveitis may show a normal or borderline ACE test. Therefore, it is important to try to make the diagnosis of sarcoid through support of high-resolution chest CT or biopsy of the eyelid or orbital tissues. If there are conjunctival granulomas, a biopsy may be helpful. In the face of negative conjunctival biopsy, an open orbital lacrimal gland biopsy, we believe, is indicated, especially if the CT scan or physical exam shows any lacrimal gland enlargement.

The treatment of orbital and adnexal sarcoid depends on numerous factors, including the presence of active systemic disease, the site and severity of involvement of the orbital tissue as well as the patient’s symptoms. Oral corticosteroids are the first line of therapy followed by intralesional injections of steroids. In cases in which steroids fail or steroid-sparing agents are required, cytotoxic agents such as methotrexate or immunomodulatory agents such as cyclosporin or azathioprine may be helpful. There is also a recent case report of monotherapy with minocycline affecting resolution of orbital and systemic sarcoidosis in a 51-year-old woman. Surgical excision is also an option for localized eyelid disease and debulking for localized orbital lesions.

The success rate with patients who have systemic sarcoid with epiphora undergoing a DCR is problematic. In these cases, at the time of DCR surgery, a diagnostic lacrimal sac biopsy should be performed with silicone stents inserted. If the biopsy is positive for sarcoid granuloma of the lacrimal sac, it is my opinion that silicone tubes should stay in indefinitely as removal will lead to DCR failure because the activity of the disease in closure of the rhinostomy site. In the event that there is a DCR failure with silicone tubes, DCR with Jones tubes will be successful (personal experience). Most patients with orbital or adnexal sarcoidosis, however, will show a good response to oral steroids.

This blog comes from a past Hyperguide Module with Ravi Berger, MD, as a co-author.