Carelli Francesco , Professor of Clinical Medicine and Elective courses in Family Medicine, University of Milan

Giotta Attilio , MD intern for family medicine, University of Milan

Inzoli Irene, MD intern for family medicine, University of Milan

Ferrario Guido, MD intern, University of Milan

While working in a GP clinic it happens to find disrespect and low regard for this branch of medicine by hospital colleagues: reports unreadable due to illegible handwriting, a careless use of abbreviations of highly specialized terms, a failure to acknowledge the work done by the colleague GP. These situations show little regard for these colleagues who, once the hospitalization finishes, will find themselves in a close and continuous contact with the patient, who rightly will ask more detailed information about his situation regarding etiology, diagnosis, treatment and prognosis. This lack of communication, which occurs in the hospital environment, can be attributed to various causes, such as, for example,  lack of time or absence of confidence with the patient, this latter problem being unlikely to be found in general practice thanks to the relationship extended over time and based on trust.

Obviously it’s not always this way: we even come in contact with colleagues who show great respect and consideration for the GP: they give due weight to the information provided as reasons for the access at their clinic, they acknowledge the work done before the patient access to the hospital, they quote in their medical records the diagnostic-therapeutic work made by the GP. All this brings a benefit to the patient: a team effort in which all the components work as one to eliminate the risk of incomprehension between colleagues, communication failures, misunderstandings, repeated tests, aiming at one goal: to cure the disease and to reach the patient well-being.

We had an example of this “ideal” situation at our clinic when a thirty year old patient came to us, having taken Loperamide after repeated attacks of diarrhea lasting for a week or so and, subsequently, reported painful swelling in the left foot with febrile episodes up to 38° C.  To reduce the symptoms the patient decided to take Diclofenac (50 mg , 3 times a day), reaching the desired effect. After the suspension of the NSAID he reported a resumption of the peaks of fever and of the pain in the foot with an involvement of the left wrist which appeared swollen, painful and limited in its movements; simultaneously he reported a modest and transient involvement of the right elbow and a sense of rigidity of the knees. All these symptoms induced the GP to make the hypothesis of a reactive arthritis. This diagnosis impelled us to act on two fronts:  therapeutic one and diagnostic one.      Regarding  the first one we prescribed Prednisone, a drug that  led to  resolution of the fever with  improvement of the clinical picture, while, regarding the diagnostic aspect, a series of assessments was suggested: x-ray of the left foot (free from structural alterations of bone and showing normal joint margins), x-ray of the left wrist (with similar finding) and blood tests (which showed  rise in ESR to 63 mm,  high CRP up to 17.6 mg / dl; WBC up to 12500; α2  globulins up to 14.8%). These findings, together with the symptoms, brought the GP to suggest to the patient a hospitalization in the Rheumatology Unit for further investigation related to a possible adjustment of the therapy. During the hospitalization several tests were performed: ECG; X-ray of pelvis, wrist, right hand, ankle and chest; US of abdomen, left and right wrist, right and left knee, ankle, foot and right and left plantar regions.   From these tests it was not possible to isolate a pathogen responsible for the enteric symptoms described at the time of the medical history and, given the link between this time and the onset of arthritis, this last was listed as an episode of reactive arthritis , as it had been previously suspected by the GP who had successfully set up an appropriate empirical therapy (a situation properly noted on the medical records). To further confirm the hypothesis properly formulated by the GP, hospital colleagues have confirmed,  during the hospital discharges, the therapy administered prior to the admission and based on Cortisone with the addition of full-dose NSAIDs  (and with its proper PPI).

This way of action, aside from demonstrating a full efficiency of integration between primary and secondary care, gives credit for the work done by the GP; it also gives the right central role of the patient in the process of diagnosis – therapy – prognosis; leading, among other things, to a good compliance by the patient, who acknowledges having had the best treatment at every stage of his disease and then follows with greater care and belief the therapeutic program offered to him.

A deepening on reactive arthritis

Reactive arthritis is defined as an acute non-purulent spondylo arthropathy complicating an infection localized in another part of the body (in most cases aero-digestive or urogenital infection). Some infections have a defined etiology (Chlamydia, Yersinia, Salmonella, Shigella, Campylobacter) and patients with reactive arthritis have HLA B27 phenotype. Other cases of reactive arthritis may occur in people who do not have the HLA B27 phenotype and may be attributable to different types of bacteria.

Reactive arthritis should not be considered as a process of active replication of a bacterium resulting in an immune response. Reactive arthritis is a pathological immune response attributable to an inadequate stimulus to whose genesis both bacteria, bacterial fragments and HLA B27 gene linked  individual  predisposition are contributing.

Individuals affected by reactive arthritis are aged between 18 and 40 years. For reactive arthritis secondary to infections of the gastroenteric tract, there is not a female-male prevalence. For reactive arthritis secondary to infections of the urinary tract the prevalence is markedly shifted toward males. The incidence of these forms is unknown (30 to 40 cases / 100,000 inhabitants per year assumed).

In most cases, these arthritis tend to resolve spontaneously. In a small number of cases they tend instead to become chronic, with clinical pictures similar to psoriatic arthritis or idiopathic spondylitis.

The pathogenesis of reactive arthritis is still unclear. Some bacterial species are most responsible for it. In synovial fluid and in articular biopsies it’s often impossible to isolate the microbe responsible by using bacterial culture techniques, it is rather usual finding some particular bacterial fragments, like lipopolysaccharide, within the joint.

These findings suggest reactive arthritis would be a process from a chronic  but subclinical infection of  synovia and enthesis. However, these events represent only the initiation of an exuberant and pathological immune reaction that leads to the acute inflammatory process. The role of HLA B27 seems to be to stimulate self-reacting clones of T cells after an inappropriate exposure to arthritogenic peptides.

In most cases  arthritis begins acutely, after 2 to 4 weeks of  urethritis or  gastro-enteritis, predominantly affecting the lower limb, with copious effusion in the knee. The arthritis is typically asymmetric, with an additional character, but rarely more than 4 joints are involved. These last are usually painful, swollen, hot, and redness may be evident, especially in locations like the distal phalanges of the hands (dactylitis). There are also frequent enthesitis of Achilles tendon and plantar fasciitis. In some subjects the back or buttocks pain can be an expression of sacroiliitis or spondylitis, late-onset clinical expressions often attributable to the uncontrolled disease’s progression.

The patient often presents systemic symptoms such as malaise, fatigue, fever and weight loss. Sometimes, in typical cases, conjunctivitis following the symptoms of  urethritis can be observed. Conjunctivitis can evolve into forms of keratitis or episcleritis. 20% of cases may be associated with erythema nodosum, described mainly in the forms associated with yersinia, in absence of HLA B27 phenotype.

In para-infectious reactive arthritis there are frequent extra-articular manifestations. Among them: gonorrheic keratoderma, characterized by the appearance of erythematous papular lesions on the soles of feet or on the palms of hands, which evolve toward the formation of a crust and the subsequent disappearance of it;  balanitis circinata with erythematous-circinate eruptions of the glans or of the penis body;  acute anterior uveitis, which can be observed in 20% of patients with prevalent HLA B27 phenotype; finally  aortitis, rarer, occurring in approximately 1% of patients.

The diagnosis is essentially clinical, since there are no laboratory data or specific radiological picture. Therefore medical history plays a fundamental role. You must invite the subject to remember a possible urinary tract infection (manifested by dysuria) or a gastrointestinal tract infection (diarrhea); it may be even useful to investigate the recent appearance of a new sexual partner. The diagnosis is not difficult when the inflammatory articular manifestations are contemporaneous or close to a clear enteric or urogenital infectious episode. The diagnosis is rather difficult when the infection is not recognized or it is pauci-symptomatic or when the time elapsed from the infection is significant, enough to make it anamnestically not easily correlated with the ongoing arthritis. In these cases the presence of an asymmetric oligoarthritis, especially in a young person, should alert the physician of the possible association with infections. Although in many cases it is unsuccessful at the time of its execution, the research of the infection focus should be implemented, on the basis of medical history and current symptoms. It is of great clinical importance to demonstrate the presence of antibodies to Yersinia, Salmonella, or Chlamydia; findings that are able to demonstrate a recent infection. You may consider: performing physical and chemical urinalysis and urine culture; a urethral and cervical swab, with subsequent cultural exams with a culture medium suitable for the research of Chlamydia; a throat swab for beta-hemolytic streptococcus; a faecal culture and a serology for germs already mentioned.

Laboratory tests performed during a reactive arthritis are demonstrative of inflammatory state with a significant elevation of ESR, CRP, fibrinogen and alpha2 globulins. There is leukocytosis and the examination of the synovial fluid shows a very high number of neutrophil granulocytes; the bacterial culture is sterile. Rheumatoid factor is usually negative. The radiographic evidence of asymmetrical  spondylitis with irregular syndesmophytes and with asymmetric arthritis of the sacroiliac joint excludes the ankylosing spondylitis in differential diagnosis. The uric arthritis is excluded for a lack of the classical crystals in synovial fluid. A further differential diagnosis must be made with gonococcal tenosynovitis, which affects equally both the upper and the lower joints, and which tends to spare the spine and to manifest itself by characteristic skin lesions.

Fortunately, reactive arthritis shows recurrences only in sporadic cases and almost always it has a course spontaneously directed to reduction of pain and resolution of swelling. However, when symptoms are very bothersome, specialists usually prescribe drugs that tend to mitigate the pain and to restore, at least partly, the functionality of the affected limbs. Indomethacin in doses ranging from 75 to 150 mg daily is the drug of first choice in the induction therapy. Phenylbutazone, 100 mg, 3-4 times a day, should be considered only as a last resort because of the potentially serious side effects. Patients with tendonitis or other enthesitis can draw benefit from intralesional steroid administration.

A series of controlled studies showed no benefit from antibiotic therapy in patients with reactive arthritis. However, early antibiotic therapy for  genitourinary tract infections caused by Chlamydia Trachomatis (with doxycycline or tetracycline) is fundamentally important .

Only in the event that a reactive spondyloarthritis tends to become chronic we can consider long term therapies with anti-rheumatic drugs: azathioprine (1 or 2 mg per kg per day) and methotrexate (7.5 – 15 mg per week). The forms of uveitis should be treated with massive doses of glucocorticoids.

Managing the disease we must include patient’s information about how to avoid sexually transmitted infections and the exposure to enteric bacteria, as well as about the appropriate use of physiotherapy.

References 

-Reactive arthritis  – Wikipedia

-Harrison, Principles of Internal Medicine, 16 ed: 2248-2250

-Zanussi, Il metodo in clinica medica, Ed Mattioli 2005, pag.112