and squamous cell carcinomas that may be increased in frequency in SS patients [6] and melanomas, the physician needs to look for cutaneous B-lymphoma and anetoderma, a condition that is frequently associated with increased risk of occult lymphoma or plasmacytoma.

18.2.2 Raynaud’s Phenomena

18.2.2.1Raynaud’s Phenomena Reported in 30% of Patients

with Primary SS

The clinical course of RaynaudÕs phenomena in most SS patients is often milder than in patients with scleroderma [6]. RaynaudÕs phenomenon is often an early sign and may be apparent before symptoms of clinical sicca are apparent. However, some SS patients do develop severe RaynaudÕs phenomenon and digital ulcers even though they lack other clinical features suggestive of scleroderma [6]. The use of protection including gloves, especially when spending excess time in the freezer section of the supermarket, and moisturizers to prevent skin cracking must be emphasized. The use of moisturizers to the Þngertips is increasingly important because SS patients spend increasing amounts of time using either their computer keyboard or Òtext messagingÓ on their cell phones (explaining in part the sudden increase in trauma pain in the thumbs used for Òkeying textÓ to other friends). Avoidance of caffeine, smoking, and herbal medications also may play a role in improvement of symptoms. The use of 3-omega fatty acids and other anti-oxidants may prove helpful [7].

18.2.2.2Pharmacologic Treatment of Raynaud’s Phenomena

Of SS patients with RaynaudÕs phenomena, about half will require pharmacologic treatment [6]. Initial therapy uses calcium channel blockers. In patients with low baseline blood pressure or symptoms of autonomic orthostatic hypotension, it is important to start dosing at low levels and increase gradually. For more severe cases,

treatment is similar to that used in PSS, including ganglionic blocks, iloprost, and use of endothelin antagonists and sildenaÞl [8Ð11].

18.3Arthralgia/Arthritis

The joint symptoms of SS frequently can be considered along the points of a square that encompasses

1.Osteoarthritis (including Òerosive osteoarthritis,Ó which may have earlier age of onset and more rapid progression);

2.Rheumatoid arthritis with its joint distribution and tendency to erosive, deforming disease;

3.Systemic lupus and JaccoudÕs-type arthritis where erosive changes on radiography are less likely even though the patient presents with typical swollen joints and also with tendon subluxation or rheumatoid-like nodules;

4.Patients may also have peripheral neuropathy and distal myopathy that contribute to their joint symptoms and require additional therapeutic modalities.

The approach to arthralgias and arthritis is similar to the SLE patients with each of the above conditions.

Symptoms are initially treated with salicylates (including disalcid or trilisate) or nonsteroidal agents (NSAIDs) of cox1 and cox2 types [2]. Many SS patients have decreased tolerance of NSAIDs, probably due to dysphagia secondary to decreased salivary ßow and esophageal motility [12]. They also have increased frequency of GERD and tracheal reßux, discussed in Chapter 16 which is exacerbated by the NSAIDs.

Among the Òslow-actingÓ drugs (previously termed disease-modifying anti-rheumatic drugs (DMARDs)), anti-malarials (hydroxychloroquine) have proven useful in decreasing the arthralgia, myalgia, and lymphadenopathy in SS patients and in tapering the steroids [13, 14]. HydroxychloroquineÕs action is similar to its beneÞt in some SLE patients, and ßare in arthralgia is noted when patients are withdrawn from their hydroxychloroquine [15]. However, many patients are unable to take hydroxychloroquine

due to difÞculty in swallowing the medication because of its bitter taste. This is particularly true with the generic form of the drug, which is often a ÒmilledÓ tablet (manufactured with a Þne dust coating of the drug still on the pillsÕ surface) with a taste quite bitter to the patient who has less saliva. The ÒbrandedÓ Plaquenil is a polished tablet and may be tolerated in patients who cannot take the generic version.

We have used hydroxychloroquine (6Ð8 mg/ kg/day) in SS patients when there is elevation of erythrocyte sedimentation rate (ESR) and arthralgias or myalgia. Indeed, hydroxychloroquine is used in SS much as it is used in SLE as a ÒplatformÓ for therapy and immune modulation of non-visceral manifestations.

In a European study, Kruize et al. [16] also found that hydroxychloroquine improved ESR and arthralgias but did not increase tear ßow volumes. When taken at the proper dose (6Ð8 mg/ kg/day), hydroxychloroquine has a very good safety record, although there remains a remote possibility (probably less than 1:1,000) [17] of signiÞcant build-up in the eye. For this reason, periodic eye checks (generally every 6Ð12 months) are recommended so that the medicine can be discontinued if there is any signiÞcant build-up.

In patients in whom arthralgia/arthritis persists, we will next use methotrexate (MTX) given as a weekly dose. We generally start at methotrexate 7.5 mg/week as an oral dose, taken with daily folic acid 1 mg. In patients where doses of methotrexate exceed 15 mg/week, we generally advise the patient to use self-injection of MTX to ensure absorption and because this minimizes gastric toxicity. Again, folic acid 1 mg/day is taken. However, the possible CNS side effects of MTX at higher dose (described by the patient as Òjust not feeling rightÓ) on the day of MTX should be checked. It is also common to use a combination of hydroxychloroquine plus methotrexate when either drug alone is insufÞcient.

In patients unable to tolerate methotrexate, our next choice is often leßunomide [2, 18]. Leßunomide is started at dose 20 mg/day. We do not use the initial loading dose of 100 mg/day

for 5 days because it leads to a greater incidence of drug discontinuation due to diarrhea or other gastrointestinal side effects. The combination of methotrexate plus leßunomide also has been used, similar to their combined beneÞts in RA patients. We check liver function tests monthly for at least the Þrst 3 months and then go to every 3-month safety checks. We advise patients about risks of alcohol and overweight patients about risks of hepatic fatty inÞltrates as co-factors in toxicity.

Previous studies in SS have utilized sulfasalazine [19] and azathioprine [20], but these agents seem less well-tolerated and less effective in SS patients than in RA or spondyloarthropathy patients [2]. In some SS patients with joint symptoms, cyclosporine has been reported [21], but the tendency toward interstitial nephritis at doses above 3 mg/kg/day in many SjšgrenÕs patients limits the usefulness of the drug.

As in SLE patients, treatment with corticosteroids is effective but limited by their usual side effects including osteoporosis, diabetes, cardiovascular, and mood disruption. However, it is worth noting that increased tear ßow, salivary ßow, and neuropathic symptoms have been reported in patients receiving relatively high-dose steroids [22]. This is important since it indicates the partial reversibility of the processes as a therapeutic goal. In patients with prednisone dose more than 5 mg/day, we add a bisphosphonate (such as risedronate) to prevent osteoporosis.

In addition to the expected problems associated with steroids, SS patients have increased problems with corticosteroids including acceleration of their periodontal disease and oral candidiasis as a result of their dry mouth. Also, it is unclear if steroids may promote accelerated atherosclerosis [23].

18.4Therapeutic Management

of Pulmonary Manifestations

18.4.1 Chronic Cough

The most common respiratory manifestation is a dry cough and hoarseness. This may be partly