This also holds true for the new non-hormonal vaginal moisturizer Replens R , which may be used unassociated with intercourse. For those patients who do not like the gel-type lubricants, there is now available Lubrin R vaginal inserts. Sterile lubricants such as Astroglide R , KY Brand R jelly, or Surgilube R are helpful (should be liberally applied to both partners for maximal comfort) [73, 74]. Unscented vaginal lubricants are preferred.

Finding the right preparation for a speciÞc individual is often a matter of trial and error inasmuch as satisfaction with each lubricant is a matter of personal preference. The patient needs to be frank with her physician regarding her satisfaction or dissatisfaction with a particular preparation. The external use of preparations containing petrolatum or oils that Òseal inÓ moisture, such as Vaseline R or cocoa butter, may lead to maceration of the vaginal lining and are to be avoided.

Vaginal dryness in perimenopausal or postmenopausal women is often related to vaginal atrophy because of declining estrogen levels and therefore responds to vaginal estrogen creams such as Estrace R . Cortisone creams are not beneÞcial in this situation.

If vaginal yeast infection occurs, prompt treatment with clotrimazole topical cream, vaginal suppositories (Gynelotrimin R ), or oral gluconazole 150 mg is safe and effective.

On the external vulvar surface, dryness may be treated with lubricating creams as would other skin surface. Several patients have reported considerable satisfaction with the use of a thin Þlm of vitamin E oil [75], used on the vulva once or twice a day.

An issue of concern to female Sjögren’s patients has been whether or not estrogen replacement therapy at the time of menopause is harmful to their condition [76]. With regards to estrogen replacement in general, the clinical evidence is controversial whether the risks of blocking osteoporosis and reducing cardiovascular mortality adequately offset the small increase in risk in breast cancer.

It is also worth noting that the subset of women who had previous hysterectomy/ovariectomy

were not found to have increased risk of breast cancer on receiving estrogen replacement [77].

Of importance, some women feel that estrogen replacement improves their quality of life in terms of mood elevation by reducing hot ßashes and hormone-related vaginal dryness [78Ð 80]. Part of this improvement may relate to the interconversion of hormones to include dehydroepiandrosterone (DHEA), which appears to have beneÞcial effects on local mucosal surfaces [81] as well as affect [82].

Earlier investigators were concerned that estrogen might have a negative influence on Sjögren’s or SLE based on animal studies. At our clinic, we have not seen any deterioration of SjšgrenÕs syndrome related to either estrogen replacement therapy or low estrogen forms of oral contraceptives.

Because of this, we encourage adequate estrogen replacement for the properly screened postmenopausal Sjögren’s patient who feels that it improves their quality of life. Although the data have not been formally collected in SS, there have been extensive trials on the use of oral contraceptives and estrogen replacement in SLE patients [78, 79, 83]. These studies have indicated safety in terms of breast cancer and disease activity. However, caution with regard to blood clot risk remains, particularly in the patient with circulating anti-coagulants or a past history of thromboembolic disease.

Nonetheless, estrogens would not be the agent of choice to deal with either postmenopausal osteoporosis or elevated lipid proÞles. Other therapeutic alternatives for osteoporosis (alendronate, Fosamax R , and risedronate, Actonel R ) and other agents for lowering cholesterol (such as statins) are now available, and estrogens are now not the agents of choice for these medical issues.

18.9Special Precautions at the Time of Surgery

SS patients have particularly unique needs at the time of surgery. These precautions are summarized in Table 17.5. Patients with ocular dryness are at increased risk for corneal abrasions

in operating rooms (that generally have low humidity) and particularly in the postoperative recovery room, where non-humidiÞed oxygen is blown across their face at a time when they are still too groggy to have adequate blink reßex.

Therefore, we have recommended application of an ocular ointment or gel prior to surgery.

Patients are subject to severe dryness of the mouth as a consequence of their disease but are told to be ÒNPOÓ for at least 12 h before surgery (and often longer if they are a later operative case in the day). We have found that patients can safely use their oral mouth sprays for comfort, while not having the risk of gastric contents and aspiration during anesthesia. If possible, patients should request from their surgeons that they be placed in an early slot in the OR schedule.

The anesthesiologist will need to take special precautions with oral intubations, as these patients have fragile teeth and often have expensive dental reconstructions including implants.

Therefore, it is important for the patient to make certain that a “heads-up” note is recorded in, or better yet, on the front of the chart.

Patients with SS often have very dry upper airways and minimal use of anti-cholinergic agents to control tracheal secretions. The tenacious mucus secretions may predispose to ÒmucusÓ plus inspissations and postoperative obstructions.

The use of humidified oxygen and mucolytics may help minimize this process.

Although anesthesiologists and surgeons are familiar with precautions regarding NSAIDs and bleeding risk, they are often less familiar with the relatively long duration of agents such as the new biologic agents. Although most of the literature about increased rate of infection after joint replacements deals with TNF inhibitors, it is likely that similar caveats will apply to additional biologic agents as they become available.

Finally, steroid coverage for “stress” levels may be required in patients on chronic steroids. Also, oral candida is quite common in the postoperative patient who has been on steroids and recent antibiotic therapy.

Patients should also be permitted to have their eye and mouth moisturizers and other appropriate remedies at bedside if inpatient.

18.10 Vaccinations in the SS Patient

Vaccine preventable infectious diseases remain a signiÞcant source of morbidity and mortality in immunocompromised hosts including SLE and SS patients, but special considerations may limit the beneÞt that this group derives from vaccination [84]. Pneumococcal, hepatitis A/B and nonlive inßuenza vaccines are recommended, particularly prior to the initiation of biologic agents. Although the antibody titers may be diminished after vaccination, the level of protection is generally considered adequate to justify the expense and risk of vaccination even after the biologic agent has been given. In the particular case of hepatitis B vaccine, experience in SLE patients has suggested the need for testing the patientÕs antibody response after two vaccinations and to determine if a third vaccination is necessary. Patients with past history of allergy (including urticarial reactions) to prior vaccines or to egg protein, it is important for the rheumatologist counsel the patient about risks. Although there are anecdotal reports of serious ßares of disease in SLE patients after vaccination, these incidents appear to be uncommon. One particular problem for the rheumatologist is the identiÞcation of the SS patient with history of neurologic manifestations including myelitis that may have had onset after a previous vaccine where chemoprophylaxis may be chosen over vaccination.

Live vaccines are generally contraindicated in immunocompromised patients including those receiving immunosuppressive medications. One of the most frequent questions for the rheumatologist is the risk/beneÞt in the use of the herpes zoster vaccine. The zoster vaccine is not licensed for use in immunocompromised people, even though this population is at especially high risk for the development of herpes zoster. This is because the group people who are mildly immunosuppressed (including patients with diabetes or who are receiving low-dose corticosteroids, tumor-necrosis-factor blockers, and other immunomodulatory drugs) were excluded from the initial zoster vaccine trials. Thus, the safety and efÞcacy of the vaccine has not been Þrmly

established patients who are at higher risk for herpes zoster. Further, the efÞcacy of the vaccine in people who have had a previous episode of herpes zoster is unknown, since this population was also excluded from the large zoster vaccine trial. Thus, there remains a debate about whether zoster vaccine is Òcost-effectiveÓ in these patients as well as potential medical-legal concerns if complications do develop.

The Center for Communicable Disease emphasizes that the level of protection is ÒpartialÓ even in non-immune compromised people. Thus, the physician needs to educate the SS patient to pursue prompt anti-viral treatment if symptoms of herpetic viral reactivation should occur even though a zoster vaccination has been given. This may be particularly important in the SS patient where the patient may mistake symptoms of a unilateral ßare of ocular pain as a result of their keratoconjunctivitis sicca or corneal abrasion. The Þnding of paresthesia (and particular a vesicular lesion) in the opthalmic dermatome should be treated promptly and requires an immediate slit lamp evaluation to determine if characteristic lesions of herpetic keratitis are present.

Among SS patients taking immunosuppressant medications (including biologic agents), no clear guidelines have been provided although experience in rheumatoid arthritis (RA) patients on biologic agents suggests beneÞt of vaccination, especially prior to initiating the immunosuppressive therapy. Another question is the SS patientÕs risk from the exposure to live attenuated ßu vaccine (LAV) or polio vaccine given to children or other family members. In clinical practice, this has not proven to be a substantial risk.

In world travelers or military personnel, the risk from yellow fever and cholera infections may be substantial. The yellow fever vaccine (usually 17D) has been well tolerated in both SLE and SS patients. Although a live cholera vaccine is available, a recombinant cholera toxin B subunit vaccine has been recommended as safe and equally effective. Unfortunately, no vaccine is yet available for dengue or Chikungunya, which remain endemic in certain parts of the world.

According to the Center for Disease Control Guidelines (http://www.cdc.gov/vaccines/), individuals with a history of allergy to prior vaccines and a history of GuillainÐBarre require careful monitoring if a vaccine is required. Also, patients with history of allergy to prior vaccines, including components grown in chicken eggs, should be given the vaccines with caution.

Patients with defects in host defense and those receiving exogenous immunosuppression agents may have suboptimal responses to certain vaccinations.

This has been demonstrated as found impaired immune responses to vaccines among patients receiving long-term immunosuppressive therapy, but postvaccination antibody titers are usually sufÞcient to provide protection for the majority of immunized individuals [85].

Vaccines against inßuenza and pneumococcus appear to be safe and immunogenic in SLE patients and their routine administration should be encouraged [86].

This is important in SLE and SS patients because many are functionally ÒasplenicÓ [87].

Patients should receive pneumococcal vaccine prior to rituximab.

CliniciansÕ concerns about adverse effects, including the possibility of exacerbating rheumatologic disease, may also limit the number of patients to whom potentially effective vaccines are offered.

The evidence for and against exacerbation of underlying rheumatologic disease and the use of postexposure prophylaxis with anti-microbials or immune globulins for selected infections have been an area of debate [88]. Although there appears to be a temporal association with some disease ßares, the causal association has not been established [89, 90].

18.11 Summary

SS presents an immense time investment to manage the unique extraglandular manifestations of SS, and these manifestations will be unique to each patient.

With rheumatologists increasingly taking the lead in being both the diagnostician and clinician managing the broad spectrum of extraglandular manifestations of SS, it is paramount that rheumatologists broaden their knowledge base of SS and its wide spectrum of extraglandular manifestations, diagnostic procedures, and therapeutic approaches.

Among the many manifestations rheumatologists can expect to see and treat include sicca symptoms (including eyes, mouth, vagina), arthralgias, myalgias, dysphagia, elevation of erythrocyte sedimentation rate (ESR), and polyclonal hyperglobulinemia, vasculitic skin lesions, pneumonitis, neuropathy, nephritis, lymphoma, interstitial pneumonitis, multifocal leukoencephalopathy, Raynaud’s phenomenon, and fibromyalgia.

18.12 Late-Breaking Updates

Botulism toxin injection may provide a novel therapy for non-suppurative parotitis due to cystic changes of the gland [91].

The unusual respiratory manifestation of pulmonary veno-occlusive disease in SS patients may respond to immunosuppressive therapy with azathioprine [92]. Another usual respiratory manifestation termed Òshrinking lung syndromeÓ associated with SS may respond to steroids and azathioprine [93]. Shrinking lung syndrome is characterized by small lung volumes, elevation of the diaphragm, and restrictive physiology without parenchymal involvement. Pleural adhesions and pain probably play a signiÞcant role in the pathogenesis.

A comprehensive review of the evaluation and treatment of pregnant patients with SS or SLE outlines the pre-natal workup and the results with therapy for those with anti-cardiolipin antibodies [94]. A high frequency of patients continuing to take medications with teratogenic potential were noted, due to inadequate counseling by physicians. Heparin plus aspirin was found beneÞcial in patients with risk for anti-phospholipid syndrome and decadron for neonatal heart block.

A retrospective study found that interstitial nephritis is more frequent than clinically diagnosed and that early recognition/treatment may slow or prevent progression [95]. In patients with suspicion of interstitial nephritis, renal biopsy was reported to be underutilized.

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