Reiter's disease in women

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<ul><li><p>335 </p><p>REITERS DISEASE IN WOMEN </p><p>DAVID L. SMITH, ROBERT M. BENNETT, and MARTHA G. REGAN </p><p>Reiters disease in its classic form is defined by the triad of arthritis, conjunctivitis, and urethritis and occurs predominantly in men. Recent descriptions have emphasized other ancillary findings: mucocutaneous le- sions, plantar fasciitis, Achilles tendinitis, sausage dig- its, asymmetrical sacroiliitis, and an association with HLA-B27. This study describes 29 women followed over the past 4 years who have a rheumatic disorder most consistent with Reiters disease. All 29 patients were seronegative, 72% presenting with an asymmetrical pau- ciarticular arthritis, and the majority evidenced lower extremity involvement. During the course of their ill- ness, 52% of the patients developed either eye and/or urinary tract involvement. Additional features were mu- cocutaneous lesions in 8 patients, heel pain or Achilles tendinitis in 15 patients, sausage digits in 20 patients, and clinical sacroiliitis in 20 patients. HLA-B27 was positive in 59% of patients, and radiographic bone and joint abnormalities were present in 52% of the patients. The recognition of this group of patients has both thera- </p><p>From the Departments of Rheumatology, Providence Medi- cal Center and the University of Oregon Health Sciences Center, Portland, Oregon. </p><p>Supported in part by the Betty Lou Margulis Rheumatology Fund, Providence Medical Center, Oregon Chapter of the Arthritis Foundation, and a Clinical Center Grant from the National Arthritis Foundation. </p><p>David L. Smith, MD: Fellow in Rheumatology, University of Oregon; Robert M. Bennett, MD, MRCP: Associate Professor of Medicine and Chief of Rheumatology, University of Oregon; Martha G . Regan, MD. Assistant Professor of Medicine, University of Ore- gon, Chief of Rheumatology, Providence Medical Center. </p><p>Address reprint requests to Martha G. Regan, MD, Chief of Rheumatology, Providence Medical Center, 700 N.E. 47th. Portland, Oregon 9726. </p><p>Submitted for Dublication June 26, 1979; accepted in revised form November I , 1979. </p><p>peutic and prognostic implications, because they prefer- entially respond to indomethacin or phenylbutazone and often pursue a chronic course, albeit without widespread joint destruction. </p><p>Reiters disease, as originally described by Hans Reiter in 1916, consists of polyarthritis, urethritis, and conjunctivitis ( I ) . Without a proven etiologic agent, Reiters disease is currently regarded as one of the rheu- matic disorders within the spectrum of the seronegative spondylarthritides (2-7). Certain associated findings have been observed to occur during the course of Rei- ters disease that often aid in the diagnosis. They in- clude skin and mucous membrane lesions, nail changes, plantar fascitis, and/or Achilles tendinitis and sausage digits (8- 12). Common investigational findings are: ra- diographic periostitis, sacroiliitis, enthesopathy, absence of rheumatoid factor, and a high prevalence of HLA- </p><p>An increasing awareness of these additional fea- tures has led to the recognition of Reiters disease in pa- tients who do not fulfill the original triad. With the ac- ceptance of a broader definition and heightened clinical awareness, the concept of incomplete Reiters disease, consisting of a seronegative oligoarticular asymmetrical arthritis without conjunctivitis or urethritis, has recently emerged (17). The features of heel pain, periostitis, and sausage digits in association with HLA-B27 were em- phasized as important adjuvant diagnostic aids. </p><p>Both classic Reiters and incomplete Reiters dis- ease appear to be a disease usually confined to men, oc- curring infrequently in women (18,19). The purpose of this study is to report 29 women with a seronegative ar- thritis most compatible with Reiters disease. </p><p>B27 (7,13-16). </p><p>Arthritis and Rheumatism, Vol. 23, No. 3 (March 1980) </p></li><li><p>336 SMITH ET AL </p><p>Table 1. Distribution of arthritis at initial evaluation </p><p>Pattern* Type of arthritic </p><p>involvement, no. patients Symmetrical Asymmetrical </p><p>Monarticular, 1 0 I </p><p>Polyarticular, 14 7 7 </p><p>Total, 29 7 22 </p><p>Oligoarticular,t 14 0 14 </p><p>* Fourteen patients had predominant lower extremity arthritis, 12 had predominant upper extremity involvement, and 3 patients had equal upper and lower extremity involvement. </p><p>t Defined as 4 or fewer inflamed joints. </p><p>PATIENTS AND METHODS Twenty-nine women were initially evaluated and fol- </p><p>lowed during the course of their disease by one of the princi- pal investigators at Providence Medical Center or the Univer- sity of Oregon Health Sciences Center. Inclusion into this series required: 1) initial objective evidence of peripheral joint inflammation; 2) one or more of the following discriminating clinical features during the course of their illness: a) nail changes either as hyperkeratosis or onycholysis, b) mucocu- taneous lesions either as keratodermia blennorrhagica or oral lesions, c) sausage digits, d) enthesopathy presenting either as heel pain, plantar fasciitis, or Achilles tendinitis, and e) clini- cal sacroiliac joint involvement. </p><p>Initial laboratory data consisted of a complete blood count, sedimentation rate (Westergren), rheumatoid factor, antinuclear factor, and urinalysis. HLA-B27 testing was per- formed on all patients. Radiographs included sacroiliac joints and symptomatic peripheral joints. Treatment with non- steroidal, antiinflammatory agents was monitored by both subjective difference in pain and stiffness and objective evi- dence of joint inflammation. </p><p>RESULTS Twenty-nine white women with a mean age of </p><p>36.7 f 13.5 years (1 SD) and age range from 13-71 years were evaluated over 2-year period. Followup was from 1 month to 4 years (mean 1.5 years). Family his- tory was negative for psoriasis, spondylitis, and other forms of inflammatory adhritis. None of the patients </p><p>gave a history of recent venereal disease exposure, sig- nificant weight loss, or antecedent dysentery. </p><p>On initial evaluation peripheral arthritis was noted in all patients (Table 1). An oligoarticular (4 joints or less) asymmetrical arthritis was present in 14 patients (48%). Polyarticular involvement occurred in 14 patients (48%) and was asymmetrical in 7. Mon- articular involvement was seen in only one patient. A lower extremity distribution predominated; arthritis was present in 104 lower extremity joints and in 90 upper extremity joints. The mean number of affected joints per patient was 6.8. </p><p>There was initial diagnostic confusion in most cases. However, ongoing evaluation revealed the ap- pearance of additional discriminating features. Fifteen patients (52%) displayed eye and/or urinary tract in- volvement. Ten of these patients (34%) had ocular in- flammation witnessed by a physician; conjunctivitis was present in 9 and iritis in 1 (this patient was B27 posi- tive). The conjunctival involvement preceded the arthri- tis by 2 months in one patient, and iritis occurred only after 3 years had elapsed in another patient. Objective evidence of urinary tract involvement occurred in 10 patients (34%) as sterile pyuria or unexplained hema- turia, occurring from 6 months prior to presentation to 2.7 years after presentation. Only 6 of these patients had dysuria. Both eye and urinary tract involvement evolved in 5 patients during the course of their illness. </p><p>At least one additional discriminating clinical feature was found either initially or on followup (Table 2). Mucocutaneous lesions occurred in 8 patients; hy- perkeratosis or onycholysis of the nails was present in 5 patients, keratoderma blennorrhagica in 5 patients, and painless oral ulceration in 1 patient. Sausage digits (Fig- ure 1) were present in 20, heel tenderness or plantar fas- ciitis occurred in 15 (Figure 2), Achilles tendinitis in 15, and sacroiliac tenderness in 20 patients (15 of whom were B27 positive). </p><p>Laboratory determinations (Table 3) revealed rheumatoid factor and ANA to be negative in all pa- </p><p>Table 2. Diagnostic features of Reiters disease in women occurring over the course of the illness </p><p>Time of documentation with reference Diagnostic features No. of patients to presentation for arthritis </p><p>Minus 2 months to 3 years Minus 6 months to 2.7 years </p><p>10 10 </p><p>Ocular involvement Urinary tract involvement </p><p>5 Presentation to 2 years Nail changes Keratoderma blennorrhagica 5 Presentation to 2.8 years Sausage digits 20 Presentation to 2 years Heel paidplantar fasciitis 15 Presentation to 2 years Achilles tendinitis 15 Presentation to 4 years Sacroiliac joint tenderness 20 Presentation to 4 years </p></li><li><p>REITERS DISEASE IN WOMEN 337 </p><p>Figure 1. Sausage digit with radiographic evidence of periositis. *Tc diphosphate shows uptake into juxtaarticular tissues. </p><p>tients. The mean sedimentation rate was 34 mm/hour. HLA-B27 was positive in 17 patients (59%). Radio- graphic abnormalities were seen in 15 patients; sacro- iliac changes were present in 5 patients, periostitis in 6 (Figure 3A), erosive joint disease in 7 (Figure 4A), and marked cartilage loss in 2 patients. </p><p>Knee arthrocentesis in 4 patients yielded syno- vial fluid with white blood counts ranging from 6,800 with 46% polymorphonuclear leukocytes (PMN) to 56,000 with 97% PMN. Synovial biopsy in 1 patient showed synovial cell proliferation with mononuclear in- filtration. Plantar fascia biopsy in 1 patient demon- strated plantar fibromatosis. Extensive keratoderma blennorrhagica was seen in 1 patient (Figure 5) who </p><p>Table 3. Investigational features of Reiters disease in 29 women ~. - - </p><p>Investigation No. of patients </p><p>Rheumatoid factor Antinuclear antibodies </p><p>Radiographic abnormalities Sacroiliac joint changes Penostitis Erosive joint disease </p><p>HLA-B27 </p><p>~~ .~ </p><p>0 0 </p><p>17 (59%) 15 (51%) </p><p>5 6 7 </p><p>also had sterile pyuria, and a skin biopsy showed changes indistinguishable from pustular psoriasis, </p><p>Indomethacin (1W200 mg) and phenylbutazone (600-800 mg) were effective in controlling symptoms and decreasing joint inflammation in 19 patients (65%); the use of other nonsteroidal antiinflammatory drugs was effective in 6 patients (20%). Healing of periostitis of the second toe (Figure 3B) and healing of an erosion of the metatarsophalangeal joint of the great toe (Figure 4B) occurred in the same patient while she was on phe- nylbutazone. A short course of 6-mercaptopurine was effectively employed to clear extensive keratoderma in 1 patient. One patient received intramuscular gold ther- apy (totaling 2,835 mg) with a good clinical result, in- cluding healing of an erosion at the interphalangeal joint of the great toe. Eight patients underwent treat- ment with corticosteroids, but in no instance was there a beneficial response. </p><p>The course of this group of patients has been characterized by three basic patterns: 1) an acute arthri- tis of short duration (3 patients); 2) a relapsing arthritis (5 patients); and 3) a chronic arthritis (21 patients). Of the 21 patients who experienced chronic disease, I 1 pa- </p><p>Figure 2. A. Sclerosis and subchondral osteopenia at the insertion of the Achilles tendon into the calcaneum-an example of entheso- pathy. B. Opposite calcaneum (uninvolved) for comparison. </p><p>Figure 3. A. Florid periostitis of the second proximal phalanx of l e right foot. B, Resolution of the periosteal reaction after 5 months ther- apy with phenylbutazone. </p></li><li><p>338 SMITH ET AL </p><p>Figure 4. A, Bony erosion at the base of the first metatarsophalangeal joint. B, Healing of the erosion after therapy with phenylbutazone. </p><p>tients had at least one period of remission and sub- sequent flare. </p><p>DISCUSSION The seronegative spondylarthritides include an- </p><p>kylosing spondylitis, enteropathic arthropathies, pso- riatic arthritis, and Reiters disease (7). Each condition is characterized by certain distinctive clinical features, and aLl exhibit some degree of axial skeleton inflamma- tion. Thus, some overlap exists between each condition, forming a disease continuum. An association with HLA-B27 has proved useful in distinguishing these seronegative arthritides from other forms of inflamma- tory arthritis (20-24). </p><p>The women in this study showed certain features characteristic of the seronegative spondylarthritides, in particular Reiters disease. The usual pattern of arthritis was most commonly asymmetrical with either oligoar- ticular or polyarticular involvement. Although eye and/ or urinary tract involvement could be documented in only 15 patients (52%), the complete triad may have been more prevalent. History for these symptoms may be difficult to elicit, since mild conjunctival imtation may go unnoticed (9). Furthermore, urinary tract in- volvement in women is difficult to specifically classify. Symptoms of dysuria are most often attributable to cys- titis or urethritis in young women; however, non-spe- cific cervicitis or mild vaginitis may also give symptoms of dysuria (26,27). The sterile pyuria is not explained in 9 of our patients, 6 of whom were symptomatic with dysuria, although a Chlamydia, T-strain mycoplasma, </p><p>or as yet unidentified infectious organism may be con- sidered a possible etiologic agent, since an association may exist between these organisms and Reiters disease (8,28,29). Hemorrhagic cystitis was seen in one patient in this study and has been described previously (1 1). The classic Reiters triad was recognized in only one pa- tient at presentation, though the complete triad devel- oped in 4 other patients up to 2.7 years after presenta- tion. </p><p>Certain distinctive ancillary features are crucial in triggering an awareness of Reiters disease. These do not necessarily occur at presentation; 19 patients (66%) developed them only on followup as long as 4 years af- ter presentation. </p><p>The term enthesopathy has been used to con- note an inflammatory process at a ligamentous bony in- sertion (9,30). This was frequently seen in our patients as Achilles tendinitis, heel tenderness, or plantar fas- ciitis. Sausage-shaped digits has been used for the clinical appearance of combined inflammation of syno- vium, tendons, and ligamentous insertions (9). Twenty </p><p>Figure 5. Extensive keratoderma blenorrhagica (seen here on trunk), the onset of which coincided with acute arthritis, sacroiliitis, and ster- ile pyuria. </p></li><li><p>REITERS DISEASE IN WOMEN 339 </p><p>patients (69%) developed sausage digits. Sacroiliac tenderness compatible with sacroiliitis was elicited on physical examination in 19 patients (65%), although ra- diographic changes occurred in only 5. These symptoms and signs may be present without radiographic change in Reiters disease (9). HLA-B27 was positive in 17 pa- tients (59%). a finding in accordance with other series on Reiters disease (3 I). Although our series is small, we could not discern a major difference between B27 posi- tive and B27 negative individuals for disease activity or clinical course. </p><p>The proper classification of patients with sero- negative polyarthritis remains controversial. In this study the diagnosis of seronegative rheumatoid arthritis is unlikely, considering the characteristic asy...</p></li></ul>