Prophylactic effect of pilocarpine on acute sialadenitis following radioactive iodine therapy in thyroid cancer patients.

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.

Botox for the prevention of radiation-induced Sialadenitis and xerostomia in head and neck cancer patients: A pilot study.

BACKGROUND: To determine the safety of Botox and its potential effect on alleviating radiation therapy (RT)-induced sialadenitis in head and neck cancer patients. METHODS: Twenty patients with stage III/IV head and neck cancer were randomized to receive Botox or saline injections into both submandibular glands (SMG). There were three visits: one before RT (V1); 1 week after RT (V2); and 6 weeks after RT (V3), each of which included saliva collection, a 24-h dietary recall, and a quality-of-life survey. RESULTS: No adverse events were observed. While the control group was much older, the Botox group more commonly underwent induction chemotherapy compared with controls. From V1 to V2, salivary flow decreased in both groups, but only in the control group from V1 to V3. CXCL-1 (GRO), a neutrophil chemoattractant, was lower in the Botox group compared with the control group at V3. CONCLUSION: Botox can be safely administered to the salivary glands prior to external beam radiation without observed complications or side-effects. After an initial reduction in salivary flow following RT, the Botox group showed lack of further flow reduction compared with controls. The inflammatory marker CXCL 1, which was reduced in the in Botox group at V3, may be a candidate for further studies of radiation-induced sialadenitis.

[Establishment and application of new techniques for submandibular gland preservation].

The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.

Protective Effect of Alpha-Lipoic Acid on Salivary Dysfunction in a Mouse Model of Radioiodine Therapy-Induced Sialoadenitis.

Radioiodine (RI) therapy is known to cause salivary gland (SG) dysfunction. The effects of antioxidants on RI-induced SG damage have not been well described. This study was performed to investigate the radioprotective effects of alpha lipoic acid (ALA) administered prior to RI therapy in a mouse model of RI-induced sialadenitis. Four-week-old female C57BL/6 mice were divided into four groups (n = 10 per group): group I, normal control; group II, ALA alone (100 mg/kg); group III, RI alone (0.01 mCi/g body weight, orally); and group IV, ALA + RI (ALA at 100 mg/kg, 24 h and 30 min before RI exposure at 0.01 mCi/g body weight). The animals in these groups were divided into two subgroups and euthanized at 30 or 90 days post-RI treatment. Changes in salivary 99mTc pertechnetate uptake and excretion were tracked by single-photon emission computed tomography. Salivary histological examinations and TUNEL assays were performed. The 99mTc pertechnetate excretion level recovered in the ALA treatment group. Salivary epithelial (aquaporin 5) cells of the ALA + RI group were protected from RI damage. The ALA + RI group exhibited more mucin-containing parenchyma and less fibrotic tissues than the RI only group. Fewer apoptotic cells were observed in the ALA + RI group compared to the RI only group. Pretreatment with ALA before RI therapy is potentially beneficial in protecting against RI-induced salivary dysfunction.

Agonist-induced 4-1BB activation prevents the development of SjÓ§gren's syndrome-like sialadenitis in non-obese diabetic mice.

Activation of costimulatory receptor 4-1BB enhances T helper 1 (Th1) and CD8 T cell responses in protective immunity, and prevents or attenuates several autoimmune diseases by increasing Treg numbers and suppressing Th17 or Th2 effector response. We undertook this study to elucidate the impact of enforced 4-1BB activation on the development of Sjögren's syndrome (SS)-like sialadenitis in non-obese diabetic (NOD) model of this disease. An anti-4-1BB agnostic antibody was intraperitoneally injected to female NOD mice aged 7 weeks, prior to the disease onset that occurs around 10-11 weeks of age, 3 times weekly for 2 weeks, and the mice were analyzed for SS pathologies at age 11 weeks. The salivary flow rate was markedly higher in the anti-4-1BB-treated NOD mice compared to the IgG-treated controls. Anti-4-1BB treatment significantly reduced the leukocyte infiltration of the submandibular glands (SMGs) and the levels of serum antinuclear antibodies. Flow cytometric analysis showed that the percentages of CD4 T cells, Th17 cells and plasmacytoid dendritic cells among SMG leukocytes were markedly reduced by anti-4-1BB treatment, in conjunction with a reduction in SMG IL-23p19 mRNA levels and serum IL-17 concentrations. Although the proportion of Tregs and IL-10 mRNA levels in SMGs were not altered by 4-1BB activation, IL-10 mRNA levels in salivary gland-draining lymph nodes and serum IL-10 concentrations were both markedly increased. While anti-4-1BB treatment did not affect the amount of Th1 cells and IFNγ mRNA in the SMGs, it increased these measurables in salivary gland-draining lymph nodes. Hence, agonistic activation of 4-1BB impedes the development of SS-like sialadenitis and hyposalivation.

Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer.

OBJECTIVE: In the current study, we examined whether selenium supplementation during iodine-131 (131I) treatment had a radio-protective effect on salivary glands. SUBJECTS AND METHODS: Sixteen patients with differentiated thyroid cancer were prospectively enrolled in the study. Patients after total thyroidectomy, before 131I treatment, were divided into two groups; 8 patients in the selenium group and 8 patients in the control group. Patients in the selenium group received 300νg of selenium orally for 10 days, from 3 days before to 6 days after 131I treatment. The control group received a placebo over the same period. To assess salivary gland function, salivary gland scintigraphy was performed before and 6 months after 131I treatment. Serum amylase and whole blood selenium levels were measured before and 2 days and 6 months after 131I treatment. Using salivary gland scintigraphy, maximum uptake ratio (MUR), maximum secretion percentage (MSP), and ejection fraction (EF) of each salivary gland were calculated. RESULTS: Baseline clinical characteristics, baseline amylase and selenium levels, and parameters of baseline salivary gland scintigraphy were not significantly different between selenium and control groups (P>0.05). On a blood test performed 2 days after 131I treatment, the selenium group showed a significantly higher whole blood selenium level (P=0.008) and significantly lower serum amylase level (P=0.009) than the control group. On follow-up salivary gland scintigraphy, the control group showed significantly decreased, MUR of the bilateral parotid and left submandibular glands, MSP of the bilateral parotid and submandibular glands, and EF of the left submandibular glands (P<0.05), while the selenium group only had a significant decrease in MSP of the right submandibular gland and EF of the left submandibular gland (P<0.05). CONCLUSION: Selenium supplementation during 131I treatment was effective to reduce salivary glands damage by 131I radiation in patients with differentiated thyroid cancer.

Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction.

Sjögren's syndrome (SS) is a debilitating autoimmune disease. Patients with SS may develop xerostomia. This process is progressive, and there are no therapeutics that target disease etiology. We hypothesized BAFF receptor (BAFFR) blockade would mitigate SS disease development, and neutralization of CXCL13 and BAFF signaling would be more efficacious than BAFFR blockade alone. We treated NOD/ShiLtJ SS mice with soluble BAFF receptor (BAFFR-Fc) or anti-CXCL13/BAFFR-Fc in combination, prior to the development of clinical disease. Our results show treatment with BAFFR-Fc reduced peripheral B cell numbers and decreased sialadenitis. In addition, this treatment reduced total serum immunoglobulin as well as IgG and IgM specific anti-nuclear autoantibodies. NOD/ShiLtJ mice treated with BAFFR-Fc and anti-CXCL13 antibody were protected from salivary deficits. Results from this study suggest blockade of CXCL13 and BAFFR together may be an effective therapeutic strategy in preventing salivary hypofunction and reducing autoantibody titers and sialadenitis in patients with SS.

Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

OBJECTIVES: To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT. MATERIAL AND METHODS: Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi). RESULTS: Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands. CONCLUSION: Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands.

Sialoadenitis secondary to ¹³¹I therapy for well-differentiated thyroid cancer.

Radioiodine (¹³¹I) is an important therapy for patients who have well-differentiated thyroid cancer. However, ¹³¹I may also result in side effects in multiple organs and glands. The glands that are frequently affected are the salivary glands with the major untoward effects including sialoadenitis and increased risk of second primary malignancy. This report will review sialoadenitis secondary to ¹³¹I therapy including (1) proposed mechanisms, (2) incidence and clinical presentations, (3) possible approaches to improve prevention, (4) management, and (5) sequelae of sialoadenitis (e.g. xerostomia and salivary duct obstruction). A discussion of second primary malignancies is beyond the scope of this review. With a better understanding of the above, dentists, oral surgeons, otolaryngologists, endocrinologists, nuclear medicine physicians, and nuclear radiologists will be more likely to implement more effective preventive measures to reduce the incidence and severity of ¹³¹I-induced sialoadenitis, and if it does occur, to identify and treat sialoadenitis sooner, thereby potentially reducing not only the severity of the initial symptoms, but also the severity of subsequent sequelae.

Salivary gland protection with sialagogues: a case study.

BACKGROUND: To decrease the severity and frequency of radiation sialoadenitis, postponement of the use of sialagogues has been proposed for the first 24 hours after (131)I treatment for well-differentiated thyroid cancer. One proposed mechanism is that sialagogues increased salivation and salivary blood flow resulting in greater radioiodine uptake in the salivary glands-a rebound effect. This case study demonstrates no rebound effect. METHODS: A 33-year-old woman with well-differentiated thyroid cancer desired to know whether she would have a rebound effect if she used sialagogues during the 24-hour period after her (131)I treatment. Salivary images of the parotid glands were initiated 2 hours after the administration of (131)I for her whole body scan. Lemon juice was administered. Background corrected time-activity curves were obtained for both parotid glands. The potential reduction in radiation absorbed dose to the parotid glands secondary to the administration of lemon juice was calculated. RESULTS: The time-activity curves demonstrated that the (131)I in the right and left parotid glands decreased rapidly after lemon juice by 87% and 83%, respectively, with return to pre-lemon juice levels by 30 and 13 minutes in the right and left parotid glands, respectively. However, at no time during the 1 hour of imaging did the uptake in either parotid gland significantly exceed the pre-lemon juice levels of activity. The potential reduction of radiation absorbed dose to the parotid glands secondary to the use of lemon juice ranged from as much as 30% to 67%. CONCLUSION: This case study demonstrates 1) an approach to assess whether an individual patient will have increased or decreased radioiodine uptake in the salivary glands after administration of sialagogues without the administration of any additional radioiodine, 2) a decrease of radioiodine uptake in the salivary glands after lemon juice without a rebound effect, and 3) a potential reduction of radiation absorbed dose with administration of sialagogues.

Botulinum toxin prevents radiotherapy-induced salivary gland damage.

Radiotherapy of head and neck malignancies results in severe damage to salivary glands. Irradiation-induced sialadenitis with xerostomia leads to a significant deterioration of the quality of life which lasts life-long. Here we show in a preliminary study that intraglandular application of botulinum toxin performed prior to radiation reduces significantly the radiation induced toxicity of the glandular tissue in rats.

Reducing the incidence of 131I-induced sialadenitis: the role of pilocarpine.

UNLABELLED: The goal of this study was to reduce the salivary symptoms of pain and xerostomia caused by 131I therapy for papillary and follicular thyroid carcinoma. METHODS: In a single-blind controlled prospective study of 60 patients, we investigated whether pilocarpine, 5 mg orally every 8 h for 1 wk after 131I therapy, would reduce salivary symptoms. All patients received 8 mg of dexamethasone and 100 mg of dolasetron mesylate orally 2 h before therapy and every 12 h for another 5 doses after 131I ingestion. In addition, for a week after therapy all drank 2,400 mL of nondairy liquid per day and had sugar-free gum or candy in their mouths at all times when awake for a week and, for the first 3 nights, every 3 h after retiring. All brushed their mouths out every 3 h while awake and also for the first 3 nights after 131I therapy. Symptoms and signs were followed by frequent telephone calls over the first week and every 8-12 wk thereafter, a physical examination within the first 10 d after therapy, and a clinic visit 6-8 mo after therapy. Statistical comparisons were by chi2 analysis. RESULTS: The 2 patient groups were not statistically different in age, sex, type of thyroid cancer, or 131I activity administered (P > 0.05). There were no statistical differences between the groups in the prevalence of sialadenitis, stomatitis, xerostomia, or dysgeusia over the next 6 mo (P > 0.05). CONCLUSION: Under the conditions of the study, pilocarpine did not reduce the occurrence of radiation sialadenitis or stomatitis. The occurrence, however, was lower than had previously been reported in the literature, possibly because of the concurrent stringent application of physiologic sialogogues (candy, gum, fluids), dexamethasone, and dolasetron mesylate, a serotonin receptor antagonist.

[Experimental substantiation of hormone replacing therapy by estrogens in treatment and prevention of inflammatory infectious diseases of maxillo-facial region].

Estrogen play the important role in normal current of inflammatory process. At age oppression of synthesis or at surgical menopause in an organism it is formed estrogen-deficiency syndrome shown in particular, in salivary glands change, loss of a jaw bones, disseminated current of inflammatory processes. For study of hormone replacing estrogen's therapy role in experiment, we determine the influence of transdermal estrogen-consisting systems on structure and function of large salivary glands, density of a bone jaws and current of infectious-inflammatory process in laboratory animals. For hormone-replacing estrogen-therapy we used an equivalent doze of estrogen-consisting plaster with a doze of estradiol 0.32 mg per day. The plaster pasted once a week on the ear. Criteria of efficiency were: calculation of bone destruction areas, pathology study of glandulars parotid and densitometries. The received experimental data testify to efficiency of application hormone-replacing estrogen's therapy in inflammatory diseases of maxillofacial area proceeding on a background of estrogen-deficiency.

Antagonist of interferon-inducible protein 10/CXCL10 ameliorates the progression of autoimmune sialadenitis in MRL/lpr mice.

OBJECTIVE: Mononuclear cell infiltration of the salivary glands is a major feature of Sjögren's syndrome (SS) and its animal model. Local generation of chemokines and the presence of chemokine receptors on the infiltrating cells may be involved in this process. We undertook the present study to investigate the expression of chemokines during the development of autoimmune sialadenitis in MRL/lpr mice and the therapeutic effect of chemokine antagonists on sialadenitis. METHODS: NH2-terminal-truncated interferon-inducible protein 10 (IP-10)/CXCL10 analogs were transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1, and injected subcutaneously into MRL/lpr mice, and the effects on sialadenitis were monitored. RESULTS: IP-10 analogs truncated by 5 or more amino acid residues from the N-terminal failed to induce chemotaxis and calcium influx by CXCR3-expressing cells. Of these, the most potent antagonist (AT) (IP-10-AT) was a molecule with methionine added after removal of the 5 N-terminal amino acid residues. Significantly increased expression of the Th1-associated chemokines IP-10, monokine induced by interferon-gamma/CXCL9, and interferon-inducible T cell chemoattractant/CXCL11 was induced in the ductal epithelium by interferon-gamma produced in the salivary glands, whereas expression of the Th2-associated chemokines thymus and activation-regulated chemokine (TARC)/CCL17 and monocyte-derived chemokine/CCL22 was almost undetectable during sialadenitis. Inoculation of IP-10-AT into MRL/lpr mice during the early stage of sialadenitis significantly reduced periductal mononuclear cell infiltration and parenchymal destruction compared with these features in control and TARC-AT-bearing mice. This was due to a significant reduction in infiltration of CXCR3+ T cells, predominantly Th1 cells, resulting in decreased interferon-gamma production. CONCLUSION: We prepared a novel potent IP-10 antagonist and demonstrated its ability to ameliorate the progression of autoimmune sialadenitis. This agent may provide a new therapeutic approach to SS.

Failure of CD25+ T cells from lupus-prone mice to suppress lupus glomerulonephritis and sialoadenitis.

The development of organ-specific autoimmune diseases in mice thymectomized on day 3 of life (d3tx mice) can be prevented by transferring CD4(+)CD25(+) T cells from syngeneic, normal adult mice. Using a d3tx model, we asked whether CD4(+)CD25(+) T cell deficiency contributes to glomerulonephritis (GN) in lupus-prone mice. New Zealand Mixed 2328 (NZM2328) mice spontaneously develop autoantibodies to dsDNA and female-dominant, fatal GN. After d3tx, both male and female NZM2328 mice developed 1) accelerated dsDNA autoantibody response, 2) early onset and severe proliferative GN with massive mesangial immune complexes, and 3) autoimmune disease of the thyroid, lacrimal gland, and salivary gland. The d3tx male mice also developed autoimmune prostatitis. The transfer of CD25(+) cells from 6-wk-old asymptomatic NZM2328 donors effectively suppressed dsDNA autoantibody and the development of autoimmune diseases, with the exception of proliferative lupus GN and sialoadenitis. This finding indicates that NZM2328 lupus mice have a selective deficiency in T cells that regulates the development of lupus GN and sialoadenitis. After d3tx, the proliferative GN of female mice progressed to fatal GN, but largely regressed in the male, thereby revealing a checkpoint in lupus GN progression that depends on gender.

Prophylaxis of radiogenic sialadenitis and mucositis by coumarin/troxerutine in patients with head and neck cancer--a prospective,randomized, placebo-controlled, double-blind study.

OBJECTIVE: To study the efficacy of coumarin/troxerutine for the protection of salivary glands and mucosa during irradiation. DESIGN: Prospective, randomized, placebo-controlled, double-blind trial. SETTING: University hospital, Germany. PATIENTS: 48 patients who had radiotherapy to the head and neck. MAIN OUTCOME MEASURES: Salivary gland scintigraphy and acute side-effects of radiotherapy (Radiation Therapy Oncology Group (RTOG) score). RESULTS: 23 patients (11 experimental, 12 placebo) completed the study. The global efficacy measure combining scintigraphy and RTOG score favoured the experimental arm (P=0.07). The RTOG score showed significantly fewer acute side-effects of radiation in the experimental arm (P<0.05). CONCLUSION: The results suggest that coumarin/troxerutine have a favourable effect in the treatment of radiogenic sialadenitis and mucositis.

Pneumoparotid: a case report and review of its pathogenesis, diagnosis, and management.

Pneumoparotid is considered to be a rare entity, but the diagnosis might not be as uncommon as reported. We report a case in which computed tomography incidentally revealed air in the parotid ducts bilaterally. Treatment is aimed at the elimination of predisposing and causative factors, but because our patient denied any symptoms or precipitating factors and had a benign presentation, no immediate intervention was initiated.

Adenoviral-mediated gene transfer to mouse salivary glands.

Adenoviral vectors effectively transfer genes to rat salivary glands. However, potent immune responses limit their use in vivo. Mice offer more opportunities than rats for the study of these immune processes. We first established conditions for infection of mouse salivary glands, with an adenoviral vector. The effects of time, viral dose, viral diluent buffer volume, and dexamethasone on expression of a transgene, luciferase, were determined by means of the recombinant vector AdCMVluc. Optimal luciferase expression was observed when the vector was suspended in 50 microL of buffer. This volume completely filled the gland parenchyma and slightly distended the capsule. Dexamethasone increased immediate transgene expression and reduced the acute inflammation one day following viral administration, but did not alter subsequent mononuclear inflammation or transgene expression 14 or 28 days later. An adenoviral vector encoding either anti-inflammatory cytokine IL-4 or IL-10 was co-administered with AdCMVluc to increase transgene expression at 14 and 28 days. While this strategy did not extend the duration of luciferase expression, co-administration of AdCMVIL-10 with AdCMVluc almost completely eliminated the chronic inflammatory infiltrate in the glands after 28 days. This study demonstrates that adenoviral-mediated gene transfer to mouse submandibular glands is possible by intraductal cannulation and that reduction of either the acute or chronic inflammatory infiltrates was insufficient to increase long-term transgene expression in this tissue.

Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjögren's syndrome?

OBJECTIVES: Prospectively collected computer database information was previously assessed on a cohort of 300 patients who fulfilled the Copenhagen classification criteria for primary Sjögren's syndrome. Analysis of the clinical data showed that patients who smoked had a decreased lower lip salivary gland focus score (p<0.05). The aim of this original report is to describe the tobacco habits in patients with primary Sjögren's syndrome or stomatitis sicca only and to determine if there is a correlation between smoking habits and focus score in lower lip biopsies as well as ciculating autoantibodies and IgG. METHODS: All living patients with primary Sjögren's syndrome or stomatitis sicca only, who were still in contact with the Sjögren's Syndrome Research Centre were asked to fill in a detailed questionnaire concerning present and past smoking habits, which was compared with smoking habits in a sex and age matched control group (n=3700) from the general population. In addition, the patients previous lower lip biopsies were blindly re-evaluated and divided by the presence of focus score (focus score = number of lymphocyte foci per 4 mm(2) glandular tissue) into those being normal (focus score 1). Furthermore the cohort was divided into three groups; 10-45, 46-60 and >/= 61 years of age. Finally the focus score was related to the smoking habits. Seroimmunological (ANA; anti-SSA/Ro antibodies; anti-SSB/La antibodies; IgM-RF and IgG) samples were analysed routinely. RESULTS: The questionnaire was answered by 98% (n=355) of the cohort and the percentage of current smokers, former smokers and historical non-smokers at the time of lower lip biopsy was not statistically different from that of the control group. Cigarette smoking at the time of lower lip biopsy is associated with lower risk of abnormal focus score (p<0.001; odds ratio 0.29, 95%CI 0.16 to 0.50). The odds ratio for having focal sialadenitis (focus score > 1) compared with having a non-focal sialadenitis or normal biopsy (focus score /= 61: odds ratio 0.36, 95%CI 0.10 to 1.43) although there was only statistical significance in the two younger age groups. Moreover, among current smokers at the time of the lower lip biopsy there was a decreasing odds ratio for an abnormal lip focus score with increasing number of cigarettes smoked per week (p trend 0.00). In the group of former smokers, which included patients that had stopped smoking up to 30 years ago, the results were in between those of the smokers and the historical non-smokers (odds ratio 0.57, 95%CI 0.34 to 0.97, compared with never smokers). Present or past smoking did not correlate with the function of the salivary glands as judged by unstimulated whole sialometry, stimulated whole sialometry or salivary gland scintigraphy. Among former smokers, the median time lapse between the first symptom of primary Sjögren's syndrome and the performance of the lower lip biopsy was approximately half as long as the median time lapse between smoking cessation and biopsy (8 versus 15 years). Hence, symptoms of Sjögren's syndrome are unlikely to have had a significant influence on smoking habits at the time of the biopsy. Among the seroimmunological results only anti-SSA/Ro and anti-SSB/La antibodies reached statistical significance in a manner similar to the way smoking influenced the focus score in lower lip biopsies. On the other hand the level of significance was consistently more pronounced for the influence of smoking on the focus score than for the influence on anti-SSA/Ro and anti-SSB/La autoantibodies. CONCLUSION: This is believed to be the first report showing that cigarette smoking is negatively associated with focal sialadenitis-focus score >1-in lower lip biopsy in patients with primary Sjögren's syndrome. Furthermore, tobacco seems to decrea