sjgren 's syndrome ( ss ) is a chronic , progressive autoimmune disease that mainly affects exocrine glands including the salivary and lacrimal glands1 )
. functional impairment of these glands by focal lymphocyte infiltration diminishes the production of tears and saliva and produces the clinical findings of persistent dry mouth and eyes .
in addition to glandular manifestations , some patients with ss have a disorder that is complicated by multiple organ involvement ; extra - glandular or systemic clinical features such as : arthritis , fatigue , lymphoma , and vasculitis may be present2 ) .
antinuclear antibody ( ana ) and rheumatoid factor ( rf ) are frequently detected in serologic tests of these patients in the course of the diagnosis of ss .
antibodies directed to extractable nuclear antigens , such as anti - ro or anti - la , are known to be more specific for a diagnosis of ss3 ) .
ss may occur as primary ss , which develops alone , or it can be associated with a variety of systemic autoimmune diseases such as rheumatoid arthritis , systemic lupus erythematosus , or primary biliary cirrhosis4 - 6 ) .
few cases of ss associated with seronegative spondyloarthropathy ( spa ) , such as ankylosing spondylitis , reactive arthritis ( rea ) , psoriatic arthritis , and undifferentiated spa , have been reported until recently7 - 9 ) .
however , most of the overlapping features have occurred in undifferentiated spa and ss , whereas ss in patients with rea is rarely reported in the literature .
we report a case of ss and concurrent chlamydia - induced rea ; this is the first report in the korean population .
a 40-year - old man presented with a history of swelling and pain of both ankle joints and plantar surfaces , and inflammatory back pain for 5 years .
the patient had a medical history of urethritis with a recurrent dysuria and pyuria , which was intermittently treated with systemic antibiotics .
a physical examination revealed significant swelling of both ankle joints and severe tenderness around the bony insertion portions of the achilles tendon .
tenderness was also noted in the : iliac crest ( bilaterally ) , tibial tuberosities , and calcaneus .
bilateral keratoconjunctivitis sicca was confirmed by an ophthalmologic examination which included the schimer 's test ( 3 mm left eye and 2 mm right eye ) .
however characteristic manifestations of rea including keratoderma blennorrhagica , circinate balanitis , and painless oral ulcer were absent .
laboratory analyses on admission demonstrated a c - reactive protein of 2.0 mg / dl ( normal : < 0.3 mg / dl ) and a erythrocyte sedimentation rate of 36 mm / hr ( normal : 0 - 20 mm / hr ) . complete blood count and blood biochemistry produced normal findings .
routine analysis and culture of urine showed pyruia ( wbc 10 - 19/high power field ) without identification of any bacterial organisms .
rf and anti - ro antibody were elevated to 56 iu / ml ( normal : < 15 iu / ml ) and 460 aau ( normal : < 150 aau ) , respectively .
however , anti - neutrophil cytoplasmic antibody , double - strand dna antibody , anti - sm antibody , anti - rnp antibody , and anti - la antibody were all negative .
igg titer for chlamydia trochomonas was 4.0 ( normal : < 0.9 ) ; this value is almost four fold elevated compared to the cut - off value using the elisa method .
the radiological finding of the sacroiliac joints revealed mild marginal irregularity and subchondral sclerosis at the left joint surface ( figure 1 ) .
in addition to periostitis , soft tissue thickening , and subchondral sclerosis along the inferior and posterior aspects of the calcaneus , bony erosion was also present at the bony insertion site of the achilles tendon ( figure 2 ) .
a whole body bone scan using tc99m - mdp showed more increased uptake at the left sacroiliac joint compared to the right joint ; in addition , increased uptake of the left foot compared to the right was observed ( figure 3 ) .
a reduced excretion or abnormal uptake of the salivary glands was not noted in the evaluation by salivary scan . on the basis of : inflammatory back pain , asymmetrical sacroiliitis , evidence of urethritis by chlamydia infection , recurrent pyuria , peripheral arthritis dominant in lower extremities , and enthesitis of achilles tendon with radiological changes , a diagnosis of rea combined with ss
the criteria were fulfilled for the diagnosis of rea based ib the european spondylarthropathy study group ( essg ) and ss of european - american consensus group , respectively10 , 11 ) . for the enthesitis and arthritis , we administered low dose corticosteroid ( prednisolone 5 mg / day ) , sulfasalazine ( 1,000 mg bid / day ) , and non - inflammatory anti - inflammatory drugs ( nsaids ) .
intra - articular injection or intra - lesional infiltration of steroid was also performed for swollen joints and tender lesions of enthesopathy . only 1 gram of oral azithromycine for urethritis was needed .
dry eyes were controlled by replacement with an artificial tear solution . the use of pilocarpine for dry mouth was withdrawn because of an erosive gastric lesion confirmed by endoscopy .
after discharge from the hospital , inflammatory back pain , swollen joints , and enthesitis subsided .
there are a few reports in the literature on concurrent spa and ss7 - 9 ) . the clinical characteristics of spa typically do not include the sicca symptoms of ss .
there are overlapping clinical and laboratory features that occur in spa ( particularly as or undifferentiated spa ) and ss .
the case of chlamydia - induced rea and ss may be the first report identified in the korean population .
central to the pathogenesis of ss is a chronic stimulation of the humoral or cellular immune system ; this includes b and t lymphocytes . circulating
organspecific autoantibodies for cellular antigens of the salivary gland are noted in patients with ss , whereas non - organ - specific autoantibodies are noted in approximately 60% of ss patients .
these nonspecific autoantibodies include rf , ana , and antibodies to the small rna - protein complexes ro / ss - a and la / ss - b ; these are the best available autoantibodies for the diagnosis of ss .
these autoantibodies may be related to functional impairment of exocrine glands by the destruction of glandular tissue13 ) .
our patient presented with the chronic , persistent sicca symptoms of dry mouth and dry eyes , showed a positive result to the schimer 's test , and showed a specific autoantibody to the ro / ss - a antigen .
our patient was diagnosed with ss without histopathologic investigation because the findings were compatible with the recently modified criteria for ss according to the european - american consensus group11 ) .
rea is a sterile inflammatory arthritis which may be triggered by a variety of urogenital or enteropathic infectious agents in the genetically susceptible host14 ) .
causative organisms identified in association with rea include the following species : chlamydia , ureaplasma , shigella , salmonella , yersinia , and campylobacter15 ) .
a well - known genetic predisposing factor is the hla - b27 type , which has been shown to be strongly related to the occurrence of a group of inflammatory arthritis conditions known as spa ; although its specific role in these disorders has not been clearly determined16 ) .
rea is typically an acute , asymmetric , and oligoarticular peripheral arthritis ; the joints affected are preferentially the joints of the lower extremities .
rea is frequently associated with one or more characteristic extra - articular manifestations such as conjunctivitis , achilles tendonitis , plantar fasciitis , dactylitis ( sausage digits ) , urethritis , circinate balnitis , and , rarely , carditis12 , 17 ) .
a positive history of recurrent urethritis and antibodies against chlamydia was observed in this case .
thus , this case also fulfilled the criteria for spa according to the essg10 ) .
rf and ana are frequently detected in patients with ss , but these autoantibodies are not considered to be a typical feature of spa . however , the frequency of reports of concurrent ss and spa have recently increased in the published literature , although this association has not been formally accepted.7 - 9 ) previous studies have examined the association between the development of ss and spa ; results have shown an increased prevalence of ss in spa with positive ana tests ; this suggests that ana may be a risk factor for the development of ss in spa8 , 9 ) .
prior studies have demonstrated that the prevalence of ana in spa is higher in patients with as and psoriatic arthritis18 , 19 ) .
recent studies have also shown that ana is increased in spa patients when compared to controls ; however , the prevalence was reported to be lower in ra patients8 , 9 ) .
although ana is common in spa patients , the specific role of ana in the pathogenesis of spa has not been elucidated .
the use of anti - inflammatory agents , including non - steroidal anti - inflammatory drugs ( nsaids ) , is the cornerstone of treatment in the management of rea.14 ) corticosteroids have also proven to be clinically valuable .
in the case of enthesis and persistent peripheral synovitis , intra - articular or intra - lesional corticosteroids are very effective .
the addition of sulfasalazine or methotrexate to suppress disease activity may be needed in patients who are refractory or can not tolerate nsaids .
long -term use of antibiotics has not been shown to be effective in controlling disease activity ; although prompt treatment with doxycycline for chlamydia infections reduced the risk of the development of rea in one study20 ) .
we chose to use azithromycin , instead of tetracycline , to control urethritis because the former agent is simple , effective and well tolerated when compared to the latter .
recently , monoclonal antibodies or receptor antagonists of tumor necrosis factor ( tnf ) such as infliximab and etanercept have been used in the treatment of rea and ss21 , 22 ) .
if a patient proves to be refractory or can not tolerate combined therapy including nsaids , sulfasalazine , and methotrexate , consideration of new biologic agents will follow .
however , the value of these biologic agents for the treatment of these diseases remains to be determined ; there is the possibility that reactivation - triggering bacteria may exacerbate disease symptoms after the administration of an anti - tnf agent . for the treatment of ss ,
, we described a rare case that presented with overlapping clinical features of chlamydia - induced rea and ss .
further study is needed to determine the nature of this apparent association between ss and spa .
 a 40-year - old korean man presented with painful swelling and tenderness of both ankle joints as well as the plantar surfaces of both feet , along with inflammatory back pain , and a purulent discharge from the urethral orifice . 
 the patient also complained of sicca - like symptoms including dry eyes and dry mouth . 
 an immunological analysis revealed a high titer of rheumatoid factor , positive results for antinuclear antibody and anti - ro antibody , and a positive result for hla - b27 . 
 an antibody titer for chlamydia was also significantly increased . 
 positive results of the schirmer 's test and for keratoconjunctivitis sicca were confirmed by an ophthalmologist . 
 these clinical manifestations were compatible with chlamydia - induced reactive arthritis ( rea ) accompanied by sjgren 's syndrome ( ss ) . 
 this is the first report of the combination of these two distinct disease entities in the korean population . 
INTRODUCTION
CASE REPORT
DISCUSSION