Management of Sjögren’s Syndrome

2.1

Dry Mouth and Salivary Gland Component

Secretory compromise in patients with SS results in heightened rates of dental caries, friability of the mucosal membranes, and fungal infections, especially candidiasis. Prevention and treatment of oral infections and the use of salivary substitutes together with stimulation of salivary flow remain the main lines of management ( Table 3.1 ).

To prevent dental caries, routine dental care and preventive dental treatment is mandatory. Administration of topical fluoride contributes to the effective mineralization of the hydroxyapatite component of the enamel, rendering it less susceptible to decay development. Stimulation of salivary flow through administration of formulations such as sugar-free lozenges, chewing gum, xylitol mannitol, and the US Food and Drug Administration (FDA)–approved oral muscarinic agonist agents pilocarpine and cevimeline is of major importance in improving oral dryness in approximately two-thirds of patients. Excessive sweating, present in half of the patients, represents the major adverse effect, with nausea, diarrhea, and palpitations being quite common. Patients who tolerate M ₂ agonists well should be encouraged to increase the daily dose for an extended period of several weeks before quitting because of ineffectiveness. In a recent report, cevimeline showed a better profile compared with pilocarpine in terms of safety profile, because primary SS patients were more likely to continue cevimeline than pilocarpine long term.

The use of local antimicrobials such as chlorhexidine in a form of varnish, gel, or rinses may be considered in SS patients with severe dry mouth and a high rate of dental caries. Nonfluoride demineralizing agents may be also considered as an adjunct therapy in xerostomic SS patients (unpublished personal observation).

The enlargement of parotid and/or other major salivary glands is asymptomatic and self-limiting in the majority of cases. For tender salivary gland enlargement, local application of moist heat and nonsteroidal antiinflammatory drugs may be beneficial. However, persistent enlargement should be meticulously evaluated to exclude bacterial superinfection and most importantly non-Hodgkin lymphoma (NHL) development.

Oral candidiasis must be treated, because it worsens sicca symptoms. It usually responds to local treatments such as clotrimazole troches and nystatin suspension. Systemic antifungal medications including fluconazole or itraconazole should be implemented in cases of extended oropharyngeal infections.

Conventional therapy with DMARDs has not proven efficacious in the management of sicca complaints. A recent randomized study on hydroxychloroquine (HCQ) administration had confirmed previous observations, showing no improvement in oral dryness features. The administration of the monoclonal antibody against CD20 rituximab has been reported to improve oral dryness, unstimulated salivary flow, and reduction in salivary gland infiltrates. These findings, however, were not confirmed in a recent randomized trial. In an interim analysis of an open-label abatacept trial in patients with rheumatoid arthritis (RA) and secondary SS, increases in saliva production by Saxon’s test were observed together with control of arthritis-related complaints. Similarly, increases in salivary production (after adjustment for disease duration) together with the reduction of lymphocytic infiltrates in the salivary gland tissues were also observed in a pilot study of abatacept in 11 primary SS patients. Nevertheless, no differences in salivary gland function were noted in a subsequent open-label study including 15 early and active primary SS patients. Blockade of the B-cell activating factor (BAFF or Blys) did not seem to improve measures of oral dryness, both subjective and objective.

2.2

Dry Eyes

Ocular dryness is one of the most devastating features related to SS. Successful management can be achieved by patient education on avoiding aggravating environmental stimuli, such as very dry or windy environments and smoking, as well as by reducing tasks associated with reduced blinking, such as reading or using monitor screens for extended periods. Systemic medications known to reduce tear secretion, such as systemic antihistamines and tranquilizers with anticholinergic effects, should be avoided. Meibomian gland dysfunction should be carefully detected and appropriately managed with eyelid margin hygiene, topical antibiotic, or systemic doxycycline therapy when required. Adhering to a diet enriched in supplemental Ω-3 essential fatty acids may reduce the severity of ocular dryness, although further confirmatory data are required for SS. In addition to preventive measures, tear replacement with topically applied artificial tears or lubricant solutions, antiinflammatory measures (eg, topical corticosteroids or cyclosporine), or oral secretagogues can be considered. When frequent use of artificial tears is required, preservative-free preparations are preferred because of the potential irritation effects of preservatives on the ocular surface. Amino acid–enriched preparations have also been shown to have beneficial effects. Compared to tear substitutes, lubricating ointments and methylcellulose inserts have longer duration but can cause a transient blurring of vision. With regard to local antiinflammatory treatment, short-term local administration of steroid, as well as cyclosporine drops (0.05%), have been convincingly shown to provide symptomatic relief, improving both subjective and objective ocular signs in a randomized controlled trial. According to recently published data, the local application of the macrolide tacrolimus (0.03% eye drops) may lead to the improvement of objective signs as early as 14 days after treatment initiation. Of interest, beneficial effects in both subjective and objective signs of oral dryness were demonstrated in 30 patients with SS, with corneal fluorescein staining scores greater than 3, and conjunctival lissamine green staining scores greater than 3, treated four times daily for 4 weeks with 2% mucin secretagogue rebamipide ocular suspension, a derivative of quinolone-class antibiotics. Additionally, administration of a single drop of cyclosporine led to improvement in eye redness, breakup time, and Schirmer test scores. Patients with residual glandular function may benefit from the oral administration of the muscarinic M ₃ receptor agonists pilocarpine and cevimeline, although the overall effects are considered less pronounced compared with alleviation of oral symptoms. Improvement of dryness scores was also observed following rituximab treatment.

Plugging of the lacrimal puncta can be offered as soon as local inflammation related to ocular dryness is controlled. For refractory cases, the use of topical autologous drops or partial closure of the interpalpebral fissure to reduce surface exposure can be alternative options. Finally, scleral contact lenses may be needed to control severe ocular surface damage.

2.3

Other Glandular Manifestations

Exocrine glands of the upper airways, gastrointestinal tract, and skin involvement can be also affected in the setting of SS, though less commonly. Desiccation of the upper respiratory tract mucosa can result into dry, crusted secretions in the nose, epistaxis, hoarseness, and bronchial hyperresponsiveness manifested as persistent dry cough and shortness of breath. A home humidifier to moisten the air and/or bromhexine at a dosage of 48 mg/day may be effective measures for alleviation of symptoms related to airways dryness, although data from controlled studies are lacking. Supportive measures such as immunization with pneumococcal polysaccharide, antibiotic treatment for sinusitis, and periodical removal of dry, crusted secretions using normal saline local infusions should be recommended. Exocrine pancreatic impairment dysfunction resulting from lymphocytic invasion of the pancreas tissue can also occur. Finally, vaginal lubricants may be used to treat vaginal dryness and dyspareunia.