one patient each with tuberculosis and sarcoidosis, which was revealed on labial salivary gland biopsy.

Symptomatic treatment included artiÞcial tears, frequent use of sips of water, and care of teeth. Corticosteroids (1 mg/kg/day to start with and later tapered over a period of 6 months) were used only in patients with glomerulonephritis and vasculitis. Immunosuppressive drugs like azathioprine or cyclophosphamide or biological agents were rarely used. Arthritis was managed with NSAIDs and low dose methotrexate (7.5Ð15 mg/week) or hydroxychloroquine (3Ð5 mg/kg/day).

Thus, in conclusion, primary SS is an underdiagnosed entity in India. Many cases are not diagnosed due to lack of awareness among physicians, ophthalmologists, or dentists who would be looking after patients with dryness of eyes or mouth. These patients receive scant attention and a prompt rheumatologist referral may help to diagnose them at an early stage. DeÞnitive primary SS with classical history of sicca syndrome is less often seen than probable cases. It is worth considering a lip biopsy and antinuclear antibody (ANA) on all patients presenting with features of sicca syndrome with systemic features like arthritis/arthralgia or Þbromyalgic

pain. Hepatitis C and HIV infection need to be ruled out.

References

1.Chandrasekaran AN, Venugopal B, Thenmozhivilli PR, Partibhan M. Spectrum of clinical and immunological features of systemic rheumatic disorders in a referral hospital in South IndiaÑSjšgrenÕs syndrome. J Indian Rheum Assoc. 1994;2:71Ð5.

2.Malaviya AN, Singh RR, Kapoor SK, Sharma A, Kumar A, Singh YN. Prevalence of rheumatic diseases in India. Results of a population survey. J Indian Rheum Assoc. 1994;2:13Ð7.

3.Misra R, Hissaria P, Tandon V, Aggarwal A, Krishnani N, Dabadghao S. Primary SjšgrenÕs syndrome: rarity in India. J Assoc Phys India. 2003;51:859Ð62.

4.Dabadghao S, Aggarwal A, Arora P, Pandey R, Misra R. Glomerulonephritis leading to end stage renal disease in a patient with primary Sjšgren syndrome. Clin Expl Rheumatol. 1995;13:509Ð11.

5.Fox RI, Saito I. Criteria for diagnosis of SjšgrensÕs syndrome. Rheum Clin North Am. 1994;20:391Ð407.

6.Vitali C, Bombardieri S, Jonsson R, et al. ClassiÞcation criteria for SjšgrenÕs syndrome: a revised version of the European criteria proposed by the AmericanÐEuropean Consensus Group. Ann Rheum Dis. 2002:61:554.

7.Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM. Clinical evolution, and morbidity and mortality of primary SjšgrenÕs syndrome. Semin Arthritis Rheum. 2000;29:296Ð304.

27.1A Disease of Antiquity in Ancient China

Historically a condition of severe dry eyes and dry mouth with glandular swelling was originally

described as “” (Zao Bi) in ancient China at around 500 BC in the medical book called Huang Di Nei Jing. It is very difÞcult to compare the clinical features of patients in antiquity with modern SS patients due to the profound

J. He ( )

Department of Rheumatology and Immunology, PeopleÕs Hospital, Peking University Medical School, Beijing, China

e-mail: hejing_1105@yahoo.com

differences in diagnosis and treatment in traditional Chinese and Western medicine. For over a thousand years, symptoms of SS have been treated by a variety of different herbal medicines provided by Traditional Chinese Practitioners (TCPs). Chinese history records the use of acupuncture and herbal mixtures such as Tea of Increased Tears in detailed records of treatments given to the emperor and his household a thousand years ago. It is likely that these herbal remedies contain a variety of cholinergic agonists and anti-inßammatory properties, similar to the use of the herbal agents including pilocarpine, quinine, and salicylates in the West.

The approach to diagnosis and treatment of SS has changed dramatically in China over the

past generation. These changes reßect the enormous changes in the health care system of China, the availability of economic resources, and increased introduction of Western diagnostic and therapeutic methods in China. These changes are the result of Chinese physicians having the opportunity to study in the West as well as the availability of Western medical literature translated into Chinese. There are also several key changes in China that have contributed to this change in clinical features and treatment of SS: (1) a generation ago, virtually all patients were seen and treated predominantly by traditional Chinese medicine practitioners with little access to Western medicine; (2) sanitation changes have altered the frequency of infections including hepatitis B, hepatitis C, tuberculosis, and EBV-related diseases (such as nasopharyngeal carcinoma that mimicked SS); (3) Western style hospitals in academic centers were previously accessible to only a very small number of patients and the clinical presentation of patients to these centers was limited to patients with life-threatening manifestations such as periodic paralysis due to renal tubular acidosis or vasculitis. This bias toward very sick patients skewed the initial distribution of patient clinical associations.

Pioneers in the evaluation of SS in China include Prof. Nai-Zheng Zang and his protŽgŽ Prof. Dong Yi in Beijing and Prof. Cheng Shunli in Shanghai who had training in Westernoriented medicine [1]. It soon became clear that the clinical manifestations in Chinese mainland SS patients were not the same as those seen among Chinese of similar genetic background

who were living in the United States, Europe, or Australia; it was deduced that environmental co-factors (such as the ubiquitous use of herbs) played a role in manifestations such as renal tubular acidosis or infections such as TBC or hepatitis viruses biased the presentations; and symptoms such as dry eyes and dry mouth were Òquality of living issuesÓ that were largely ignored a generation ago against the background of providing treatment for life-threatening manifestations even when patients were seen in Western style academic institutions. As showed in studies by Doctors Nai-Zheng Zhang and Yi Dong and Chen Shun-li in early 1980s, the prevalence of SS was 0.77% by Copenhagen criterion and 0.33% by Fox criterion, respectively [2].

Even today outside large urban medical centers in China, SS is not a well-recognized disease and traditional medicine remains the mainstay of health care in the rural regions of China and for many patients in large urban centers. As demonstrated in a survey carried out recently by our group, only 37.9% of SS patients attended rheumatology clinic at their Þrst visit to hospital. Most of the SS patients tended to consult with hematologists, stomatologists, gastroenterologists, or doctors practicing traditional Chinese medicine. It is not surprising that SjšgrenÕs syndrome is often diagnosed with delay or misdiagnosed, which is largely due to unawareness of the disease by public as well as the atypical clinical features [3].

As shown by a survey including 224 Chinese SS patients, there are many different manifestations and patients are seen by multiple specialties (Tables 27.1 and 27.2) [3, 11]. The

Table 27.2. Complications of 224 SjšgrenÕs syndrome patients

most common symptoms include leukopenia (33%), arthritis (25%), and RaynaudÕs phenomena (16.5%). Interestingly, it appears that SS-associated leukopenia is more common in Chinese patients than that in Western countries. In contrast, there is less RaynaudÕs phenomena in Chinese patients. In addition, thyroid dysfunction is one of the major complications in Chinese SS patients. The prevalence is up to 44.4% in a large-scale study, including hyperthyroidism, hypothyroidism, and thyroxin abnormality [4].

Another recent study by An et al. in our group focusing on SS in youth has shown that parotid gland swelling, hematological involvement, and hyperglobulinemia were much more common in early-onset SjšgrenÕs syndrome [5].

It has been shown that a portion of patients developed lupus shortly after SS (SS-onset lupus), while others might suffer from SS and lupus almost at the same time. In 2006, Jia et al. from our group studied the clinical and serologic features of 22 SS patients associated with systemic lupus erythematosus (SLE) [6]. It was found that 36% (8/22) of patients were SSonset SLE, 32% (7/22) of patients developed SS and SLE simultaneously, while the other 32% (7/22) were lupus-onset SS. The ages at onset of SLEÐSS were older than SLE and younger than SS. Another study in China showed that SSÐSLE patients with distinctive clinical manifestations and favorable prognosis require less glucocorticoids and immunosuppressants [7].

27.2“A Light in Darkness”—Value of Novel Autoantibodies

in Diagnosis of SS

It has been a long time that rheumatologists puzzled in the diagnosis of SS, the ÒunclearÓ and ÒmisleadingÓ syndromes. This is partially owing to patientsÕ reluctance to have a labial gland biopsy and low speciÞcity and lack of ready availability of anti-SSB and anti-SSA antibody tests. In recent years, the role of anti-α(alpha)- fodrin antibody in diagnosing SS has been studied extensively by our group and others have been explored in China [3, 11].

In addition, several studies in China have suggested the diagnostic value of a novel anti-M3 receptor (M3R) antibody in SjšgrenÕs syndrome. Fang et al. from our group have shown that antiM3R is probably a serologic biomarker in SS with a sensitivity of 91.3% and a speciÞcity of 84.6%. Our recent study showed that antibodies against a peptide derived from the second loop of M3 receptor are valuable in the diagnosis of SS with sensitivity at 62.2% and speciÞcity at 95.1%, respectively. The anti-M3R antibodies were detected in most of the SS patients lacking anti-SSB or anti-SSA. These data indicated that anti-M3R might be of signiÞcance in diagnosis of SS. However, our studies are limited by the absence of salivary gland biopsies that serve as the Ògold standard.Ó

27.3“Pearls” of Chinese Medicine

Treatment of SS in China is much the same as that in Western countries [8]. Most patients with mild disease are treated symptomatically with eye drops, mouth syrup, and nose syrup, while patients with systemic involvement might be put on with corticosteroid or immunosuppressant, such as cyclophosphamide, azathioprine, or leßunomide. Biological agents including rituximab are occasionally used under certain restricted conditions, e.g., severe thrombocytopenia.