Factors separate Sjögren’s syndrome from simple dry eye

Decreased corneal innervation can result from reduced lacrimation and tear clearance, further aggravating the condition.

Patients with Sjögren’s syndrome have severe dry eye, but they have much more than just that ocular symptom. A number of factors must be evaluated to make a definitive diagnosis, according to one Madrid-based ophthalmologist.

“It has been always thought that Sjögren’s syndrome is … dry eye. That is true, but Sjögren’s syndrome patients have a higher occurrence of meibomian gland disease. So they have also an autoimmune dry eye,” said Jose Manuel Benitez del Castillo, MD, during a presentation at the European Society of Ophthalmology meeting in Madrid.

Dr. Benitez del Castillo discussed how to differentiate Sjögren’s syndrome from other forms of immunopathic dry eye.

Because Sjögren’s syndrome is different from other forms of dry eye, he said, it requires different treatment. However, diagnosis requires recognizing several signs and symptoms, which can vary among patients.

Further complicating the matter, the signs and symptoms of Sjögren’s syndrome vary in the literature, and even between international communities.

He said criteria used in the United States are more restrictive compared to criteria used by European surgeons. But a consensus between U.S. and European authorities was published by Dr. Vitali and colleagues in 2002, he said.

Primary, secondary Sjögren’s

According to Dr. Benitez del Castillo, Sjögren’s syndrome manifests in two forms — type 1, or primary, and type 2, or secondary.

He said the criteria used to diagnose primary and secondary Sjögren’s syndrome are similar. He said the main difference is that primary Sjögren’s is not related to other collagen vascular diseases, such as rheumatoid arthritis, “but the severity of dry eye is similar in both types.”

For a diagnosis of primary Sjögren’s syndrome, a positive biopsy showing autoantibodies of the types consistent with the disease is required, he said.

Medications can affect dry eye

Pharmacological dry eye is normally mild, but it can exacerbate age-related dry eye. This underscores the importance of taking a thorough patient history. Jose Manuel Benitez del Castillo, MD, said medications can affect dry eye via two mechanisms — by decreasing the production of tears by the lacrimal gland or by producing ocular surface disease. He said some drugs can lead to a decrease in tear production. These include sleeping pills, diet pills, diuretics and some drugs for hypertension. Other drugs can result in ocular surface disease via the epitheliopathy, including topical anesthetics, some antibiotics and topical beta blockers. It is important to ask patients about their medication use because it may affect the dry eye diagnosis, he said. For example, vitamin A derivatives, used to treat acne, can produce dry eye and blepharitis. “It is important to take that into account when we have a ... teenager with dry eye. We have to think about that and ask the patient if they use this type of drug,” he said.

Additionally, at least four of six signs and symptoms must be present. These include dry eye symptoms with or without artificial tear use, dry mouth symptoms, Schirmer 1 test, positive minor salivary gland biopsy, nonstimulating total sialometry and salivary gammagraphy or sialography.

The symptoms must also be present without cervical radiotherapy, hepatitis C virus infection, AIDS, lymphoma, sarcoid, graft-versus-host disease and anticholinergic use, he said.

The criteria used to diagnose secondary Sjögren’s syndrome are similar to those for the primary form, but they are related to other collagen vascular disease, he said.

Patients with Sjögren’s syndrome have autoantibodies that act against cholinoreceptors, found at the level of the lacrimal gland, he said.

“Patients with primary and secondary Sjögren’s, they have a higher degree of this autoantibody against these receptors in comparison with non-Sjögren’s disease, normal patients and even patients with rheumatoid arthritis but without Sjögren’s,” he said.

In addition, he said, patients with Sjögren’s syndrome have more severe dry eye. Lactoferrin produced by the lacrimal gland is also decreased compared to patients with non-Sjögren’s dry eye disease, such as meibomian gland disease.

Patients with ocular perforations may also have a higher degree of matrix metalloproteinease compared to patients with normal eyes or normal meibomian glands, he said.

Lacrimation and tear clearance

In addition to reduced tear production, patients with Sjögren’s syndrome have a decrease in tear clearance, Dr. Benitez del Castillo said. This results in inflammatory mediators remaining on the ocular surface and causing more inflammation, which causes decreased innervation at the lacrimal gland.

“There is inflammation in the ocular surface of these patients. Those inflammatory markers are increased in patients with Sjögren’s syndrome,” he said.

He said he and colleagues recently used confocal microscopy to evaluate the corneal innervation in a patient with Sjögren’s syndrome.

He said the patient did show decreased innervation of the cornea, even though the cornea had a normal basal plexus.

“It can explain several things. For example … the sort of dry eye disease this patient has is idiopathic because of the absence of tropic stimulation of the epithelium,” he said.

“It is important to keep in mind that we can use anti-inflammatory drugs to treat this disease — corticosteroids or cyclosporine,” he said.

Dr. Benitez del Castillo said it is also important to perform Schirmer testing with anesthesia and nasal stimulation to aid in diagnosis and treatment of the disease.

“We have to think [about what] the lacrimal gland secretion provides … that are needed to protect the ocular surface from blinking and different trauma that we are exposed to every day at every minute,” he said, noting such substances as fibronectin and vitamin A.

Regarding treatment, he said secretion of deficient lacrimal substances can be stimulated using pilocarpine or replaced using drops of autologous serum.

For Your Information:

• Jose Manuel Benitez del Castillo, MD, can be reached at Policlínico Ruber, Maldonado 50, Madrid 28006, Spain; +(34) 91-40-11-800; fax: +(34) 91-40-20-921; e-mail: jbs00004@teleline.es.

Reference:

• Vitali C, Bombardieri S, et al. Classification criteria for Sjögren’s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61(6):554-558.