[A Case of Reactive Arthritis after BCG Intravesical Infusion Therapy Successfully Treated with Salazosulfapyridine].

The patient was a 70-year-old woman who underwent transurethral resection of bladder tumor in May 2020. She was diagnosed with urothelial carcinoma (high grade, pT1 by pathology). We started bacillus Calmette-Guerin (BCG) intravesical infusion (80 mg Tokyo strain) in August of the same year after a second transurethral resection. Pain during urination persisted during the administration of BCG, and it worsened after the completion of six doses. The patient was hospitalized with back and neck pain and difficulty in physical movement. At the time of admission, bilateral conjunctivitis was observed. The patient was diagnosed with reactive arthritis associated with BCG intravesical injection therapy, as three typical symptoms were observed (bilateral conjunctivitis, urethritis, polyarthritis). The patient was treated with prednisolone and non-steroidal anti-inflammatory drugs for arthritis, but the symptoms did not improve. We administered salazosulfapyridine and her reactive arthritis improved.

An overview of reactive arthritis.

Reactive arthritis, also known as Reiter syndrome, is a spondyloarthropathy that typically follows a urogenital or gastrointestinal infection, and is characterized by conjunctivitis, urethritis, and arthritis. The frequency of reactive arthritis in the United States is estimated at 3.5 to 5 patients per 100,000. Physician assistants (PAs) can manage the condition; therefore, they should be familiar with the disease's signs and symptoms, diagnostic criteria, and treatment regimens. Without proper management, reactive arthritis can progress to a chronic destructive arthritis. Prompt recognition of the condition is key to early intervention and a better patient outcome with fewer complications.

Enigmatic question of early reactive arthritis disclosed after researches of mycoplasmas, Chlamydia trachomatis and enteropathogens following the holistic vision of human being.

An HLA-B27 genetic profile patient is fully investigated by molecular analyses after an anamnestic assessment of multi-site ecosystems, following the holistic vision of human being.VDRL and Widal-Wright (WWR) resulted positive, showing at Wright’s reaction a title of 1:40. Of all the enzymatic activities measured, only the ALP enzymatic pool activities showed a low increasing value of 297 U/L. Of all later acute phase proteins, Only C3 c protein value (127 mg/dL) and fibrinogen (376 mg/dL) were altered. Cultural and molecular oropharyngeal ecosystem investigation resulted significantly positive to Mycoplasmas(Mhand Uu) and Chlamydia trachomatis(Ct) together with a spread of saprophytic flora. From an accurate anamnesis, several and severe uro-genital clinical symptomatology emerged from birth until the beginning of rheumatologic symptomatologies that were confirmed by oldest Mh, Uu and Ctsilent chronic infections between these ecosystems. The molecular HPV research was negative, while the Thin prep pap-test was indicative of vaginosis and cellular reactive changes associated with inflammation. Parasitological research resulted positive for presence of 5-7 newly-formed G. lambliacysts for microscopic field, while digestibility test was positive for presence of several free fatty acid crystals. The remarkable presence of indigested meat fibre and several mucous dense filaments were observed. The pH value was 6.5, while blood faecal test was positive. The values observed were: ferritin 12 microg/L (10-120), total iron-binding capacity (TIBC) 310 &mgr;g/dL (300+-20), unsaturated iron-binding capacity (UIBC) 286 microg/dL (200-220) and iron seric level 24 microg/dL (60-130). Faecal research highlighted a very scarce presence of E. coli, resulting in 102 UFC/g of stool. Of all enteroinvasive pathogens, researched by molecular analyses, only Yersinia spp. was positive. After several specific cycles of antibiotic and antinflammatory therapies, the patient improved its general health condition considerably and showed almost complete regression of aching inguinal lymph node inflammation. In a picture of a worsening inflammatory process, produced by pathogens like Mycoplasmas, chronic silent or low grade inflammation atypical agents, in young HLA-B27 positive patient, VDRL test resulted positive. This value represents the first non-specific unique spy to reveal the precocious immunological signal in order to register the beginning of early innate immune system decay, keeping in mind that mycoplasmal and chlamydial infections are the triggering of cancer in patients genetically susceptible.

Reiter's disease treated with Nux vomica.

We report the case of a 35 year-old man suffering from Reiter's disease. He did not respond to Lycopodium or Nux vomica in medium dilutions, but did respond to Nux vomica in very high potency.

Biological therapies in the spondyloarthritides--the current state.

Therapeutic options for patients suffering from the more severe spondyloarthritides (SpA) have been rather limited in the last decades. Evidence is now accumulating that anti-tumour necrosis factor (TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published concerning more than 1000 patients with AS and PsA, this treatment seems to be even more effective than in rheumatoid arthritis (RA). The anti-TNFalpha agents currently available, infliximab (Remicade), etanercept (Enbrel) and adalimumab (Humira), are approved for the treatment of RA in the USA and Europe. The situation for SpA is different from RA because there is an unmet medical need, especially in AS, since no therapies with disease-modifying anti-rheumatic drugs (DMARDs) are available for severely affected patients, especially those with spinal disease. Thus, TNF blockers may even be considered a first-line treatment in a patient with active AS and PsA whose condition is not sufficiently controlled with non-steroidal anti-inflammatory drugs (NSAIDs) in the case of axial disease, and sulphasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg is required, and intervals of between 6 and 12 weeks are necessary to constantly suppress disease activity-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are almost no studies yet on adalimumab (standard dose in RA, 20-40 mg subcutaneously every 1-2 weeks) in SpA. Infliximab and etanercept are now both approved for AS in Europe. The efficacy of etanercept was first demonstrated in PsA, and it is now approved for this indication in the USA and Europe. There is preliminary evidence that both agents also work in other SpA, such as undifferentiated SpA (uSpA). Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can largely be prevented by appropriate screening. As it stands now, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.

Long-term progression, prognosis, and treatment of patients with recurrent ocular manifestations of Reiter's syndrome.

PURPOSE: To investigate the spectrum of ocular involvement, to examine the clinical outcome, and to analyze the influence of treatment in patients with chronic ocular manifestations of Reiter's syndrome (RS) referred to a tertiary care ocular immunology service. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twenty-five patients with RS evaluated at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1981 through 2001. METHODS: Charts of patients were reviewed and data on age, gender, follow-up time, ocular symptoms, extraocular involvement, ocular complications, therapy, and visual acuities were recorded. MAIN OUTCOME MEASURES: Visual acuity, ocular complications, disease progression, clinical outcome, and systemic treatment. RESULTS: Twenty-five patients (20 male and 5 female) diagnosed with RS, with a mean age at presentation to our service of 37 years, were studied. The mean follow-up was 48.5 months. Eighty-five percent of patients tested were positive for human leukocyte antigen B27. Sixty-four percent of patients had a positive family history. All patients had oligoarthritis and enthesitis, most commonly affecting the back (56%), Achilles tendon (52%), and sacroiliac joint (24%). Eighty percent had a history of infection, most frequently urethritis (68%). Forty-four percent had a history of mucocutaneous lesions. All patients demonstrated ocular involvement at the time of diagnosis (68% with unilateral and 32% with bilateral disease), 84% had evidence of uveitis, 3% had scleritis, 2% had conjunctivitis, and 1% had pars planitis and iridocyclitis. During follow-up, the ocular complications included conjunctivitis (96%), anterior uveitis (92%), posterior uveitis (64%), keratitis (64%), cataract (56%), intermediate uveitis (40%), scleritis (28%), cystoid macular edema (28%), papillitis (16%), and glaucoma (16%). Systemic treatment for ocular inflammation was initiated in all patients. Ninety-six percent were treated with nonsteroidal anti-inflammatory agents. Eighty-eight percent were treated with corticosteroids, 64% requiring systemic prednisone. Immunosuppressive therapy was initiated in 52% of patients, with all receiving methotrexate. Seven patients required more than one immunosuppressive agent. The mean initial visual acuity was 20/25 in the right eye and 20/30 in the left eye. The mean final visual acuity was 20/25 in the right eye and 20/25 in the left eye. CONCLUSIONS: Reiter's syndrome may be associated with chronic recurrent ocular inflammation. Systemic therapy (including immunosuppressive treatment) typically is required to control the ocular inflammation and to prevent progressive visual loss.

Effect of a three month course of ciprofloxacin on the late prognosis of reactive arthritis.

BACKGROUND: The value of antibiotics in the treatment of reactive arthritis (ReA) is still controversial. OBJECTIVES: To analyse the long term outcome of patients with ReA, treated with a three month course of ciprofloxacin or placebo. METHODS: Patients who had had ReA and had participated in a double blind, placebo controlled trial on the effectiveness of ciprofloxacin 4-7 years earlier were invited to a clinical examination. Of the 71 patients who were included in the original study, 53 agreed to visit the clinic for an examination. Twenty six of 53 patients had originally received ciprofloxacin and 27 had belonged to the placebo group. Of these, 20 in the ciprofloxacin and 25 in the placebo group were HLA-B27 positive. RESULTS: 11/27 (41%) patients in the original placebo group had now developed chronic rheumatic disease, as compared with only 2/26 (8%) patients originally treated with ciprofloxacin (p=0.006). Two patients who originally had received placebo, none in the ciprofloxacin group had developed ankylosing spondylitis, and three patients in the original placebo group, none in the ciprofloxacin group had recurrent anterior uveitis. The same tendency was seen when several different measures were analysed. Of the patients with chronic spondyloarthropathy, 10 in the placebo and none in the ciprofloxacin group were HLA-B27 positive. CONCLUSION: Analysis 4-7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis.

Ciprofloxacin v placebo for treatment of Yersinia enterocolitica triggered reactive arthritis.

Patients with yersinia triggered reactive arthritis were double blind randomly allocated to receive treatment with ciprofloxacin 500 mg twice daily orally or placebo during three months. The diagnosis was made by serology (specific IgA and IgG antibodies to yersinia outer membrane proteins (yops)), positive culture, and/or demonstration of Yersinia enterocolitica antigen in colon biopsy specimens. Patients were evaluated monthly during and after treatment up to 12 months. Of 18 patients enrolled, all could be evaluated for safety, 16 for efficacy. There was a tendency towards faster remission and relief of pain in those receiving ciprofloxacin. Y enterocolitica was eliminated from the gut associated lymphoid tissue in six of seven patients receiving ciprofloxacin compared with none of nine patients receiving placebo. Patients receiving placebo had more and prolonged circulating IgA antibodies against yops than patients treated with ciprofloxacin.

Chronic destructive oligoarthritis associated with Propionibacterium acnes in a female patient with acne vulgaris: septic-reactive arthritis?

Propionibacterium acnes is an anaerobic bacillus implicated in certain chronic arthritides. This report describes an HLA-B27+ 17-year-old woman with acne vulgaris who presented with rapidly destructive arthritis in the left shoulder as well as an evolving left subclavicular adenopathy. One year later, arthritis was detected in the left knee; the inflammatory synovial fluid was sterile. Growth of P acnes was observed in cultures of the shoulder synovium and lymph nodes, but polymerase chain reaction was negative for Borrelia, Chlamydia, and Ureaplasma DNA. Three months of treatment with amoxicillin and rifampicin led to clinical disappearance of the oligoarthritis, but arthritis recurred in the left knee after discontinuation of therapy. On biopsy, bacteria were undetectable in the knee synovium, but chronic arthritis was evident histologically. Antibiotics were reintroduced for 12 months and were again effective against the clinical symptoms. Although the asymmetry, histologic features, arthritis-acne association, and genetic predisposition of this chronic destructive oligoarthritis would seem to indicate a reactive arthropathy, the isolation of P acnes from 2 distinct specimens prompted us to propose calling this a case of septic-reactive arthritis, which is further supported by the absence of progression after antibiotic therapy and the persistence of the rheumatism. To our knowledge, this is the first demonstration of the efficacy of prolonged antibiotic therapy on the joint manifestations of chronic rheumatism associated with acne.

Ciprofloxacin treatment does not influence course or relapse rate of reactive arthritis and anterior uveitis.

OBJECTIVE: To assess the efficacy of ciprofloxacin in the treatment of reactive arthritis (ReA) and anterior uveitis (AU) in a double-blind, randomized, placebo-controlled trial. METHODS: Seventy-two patients participated in this study, 56 with ReA and 42 with AU (26 patients had both ReA and AU). Ciprofloxacin (750 mg twice a day) was administered for 12 months with a 12-month followup. End points of the study included time to disease relapse and measures of disease severity. RESULTS: There was no difference between groups in time to disease relapse, joint inflammation, number of joints and enthesis involved in patients with ReA, or signs and symptoms of AU. CONCLUSION: Long-term treatment of ReA and AU with ciprofloxacin made no statistically significant difference to the natural history of these diseases or their severity.

No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Safety of long-term therapy with ciprofloxacin: data analysis of controlled clinical trials and review.

We reviewed the literature and the manufacturer's U.S. clinical data pool for safety data on long-term administration of ciprofloxacin (Bayer, West Haven, CT). Only controlled clinical trials including patients treated for >30 days were selected. We identified 636 patients by literature search and 413 patients in the Bayer U.S. database who fulfilled our search criteria; the average treatment duration for these patients was 130 and 80 days, respectively. Main indications for long-term therapy were osteomyelitis, skin and soft-tissue infection, prophylaxis for urinary tract infection, mycobacterial infections, and inflammatory bowel disease. Adverse events, premature discontinuation of therapy, and deaths occurred at a similar frequency in both treatment arms. Most adverse events occurred early during therapy with little increase in frequency over time. As with short-term therapy, gastrointestinal events were more frequent than central nervous system or skin reactions, but pseudomembranous colitis was not observed. No previously unknown adverse events were noted. We conclude that ciprofloxacin is tolerated as well as other antibiotics when extended courses of therapy are required.

Actinomycotic splenic abscesses presenting with arthritis.

An 18-month-old Caucasian female began with a high fever. She developed swelling in one finger and one toe. Abdominal ultrasound revealed multiple abscesses in her spleen. Multiple blood culture and splenic abscess aspirations grew no pathogens. She had transient response to multiple antibiotics and splenic abscess drainage, but fever returned along with subcutaneous nodules. Culture of splenic tissue from her second splenic drainage eventually grew one organism identified as Actinomyces naeslundii. Therapy with high dose penicillin followed by amoxicillin p.o. and total splenectomy led to complete recovery.

Are antibiotics of any use in reactive arthritis?

In the pathogenesis of reactive arthritis, infection through the mucosal route and genetic susceptibility (HLA-B27) are the most important contributing factors. With regard to non-specific urethritis, most probably caused by Chlamydia trachomatis infection, the use of early antimicrobial therapy has been shown to be effective in preventing arthritic recurrences. When the arthritis has been initiated, short-term conventional antimicrobial therapy seems unable to modify the course of the ongoing disease. In patients with acute reactive arthritis, a prolonged (3-month) treatment with tetracycline shortens the duration of arthritis when triggered by Chlamydia trachomatis, while such treatment has not proved effective in enteroarthritis. In patients with chronic reactive enteroarthritis, a prolonged course of quinolones, such as ciprofloxacin, might be of benefit. Sulfasalazine, which has an effect in the acute exacerbations of ankylosing spondylitis, is probably also effective in chronic reactive arthritis. An antimicrobial effect can be one of the mechanisms by which sulfasalazine exerts its therapeutic effect. Follow-up studies are necessary to assess the influence of antibiotic therapy on the late prognosis of patients with reactive arthritis.

Effect of antimicrobial treatment on chronic reactive arthritis.

In a double-blind study comprising 36 patients the effect of a three-month course of ciprofloxacin on chronic reactive arthritis was evaluated. At the end of the follow-up period 6 months after stopping the therapy, arthralgia, pain at movement and morning stiffness had decreased significantly compared to the values before the treatment in the ciprofloxacin group, whereas the Ritchie index and ESR showed a significant decrease in the control group. We conclude that further studies are necessary before the value of prolonged ciprofloxacin treatment of chronic reactive arthritis can be established.

Influence of antibiotics on IgA and IgG response and persistence of Yersinia enterocolitica in patients with Yersinia-associated spondylarthropathy.

The IgA and IgG antibody response to plasmid-encoded outer membrane proteins was studied in 59 patients with yersinia-associated spondylarthropathy during 15 months of follow-up. Initially, all patients had specific IgA and IgG antibodies to the 36 and 46 kDa and 30% also to the 26 and 58 kDa released proteins, which correlated with the finding of virulent Yersinia bacilli in intestinal biopsies. IgA disappeared in 69% of untreated patients after nine months and persisted in 31% after one year. IgA disappeared within three to six months in 81% of the patients treated with antibiotics for four to six weeks and persisted in 6% after one year (p less than 0.002). IgG antibodies to the 36 and 46 kDa outer membrane proteins persisted in 80% of all patients. Disappearance of IgA was coupled with disappearance of yersinia from intestinal biopsies.