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Case III RA
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Anggelfire Basic RA 3

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During her initial rheumatology clinic visit, a thin, pale 60-year-old Caucasian woman related the following history: Approximately 4 years ago, she began to have pain in both hands and noticed mild swelling of several joints. She also noticed morning stiffness, which usually resolved by the time she arrived at her job as a cashier in a local market (about 1 hour later). She tried over-the-counter medications - ibuprofen and acetaminophen - which did not provide much relief. She then consulted her primary care physician (PCP) who prescribed diclofenac sodium, 75 mg bid. The PCP ordered lab tests, but no x-rays.
 
The patient returned to the PCP 3 weeks later and reported some improvement in her symptoms. She learned that her test for rheumatoid arthritis was negative but her "sed rate was just a little bit high." The PCP prescribed prednisone 5 mg daily in addition to diclofenac sodium. She felt considerably improved and did not return for continuing care. She eventually was well enough to take these medications on a PRN basis.
 
She continued to do well for the next 2½ years, tolerating some morning stiffness and a variable degree of pain and swelling, which responded adequately to prednisone and ibuprofen. She saw her PCP only to refill her prednisone prescription.
 
At this time, she began to notice increasing pain and stiffness, which was not relieved by the medications she had on hand. After approximately 2 months of worsening symptoms, she saw a new PCP, who noted swollen and tender wrists and metacarpophalangeal (MCP), proximal interphalangeal (PIP) and metatarsophalangeal (MTP) joints. He gave her a prescription for naproxen 500 mg bid and referred her to the rheumatology clinic for evaluation. No lab studies or x-rays were done.
 
Social history revealed that she was born in Europe and emigrated with her mother to the United States at age 15. After graduating from high school, she held numerous jobs primarily as a  clerk. She had a short lived and childless marriage. She lives alone and is self supporting.
 
She gave a history of pain, stiffness, and swelling in both hands and wrists and reported difficulty with grooming and dressing. She has difficulty combing her hair and feels pain putting her hands behind her back to hook her bra. She also has pain in her groin when putting on her right stocking. Recently, she has been getting into her car by backing herself into the driver's seat and turning her body forward into the driving position. She has pain in her feet while standing or walking, fatigues easily, and has difficulty completing her usual work shift. She began to miss work due to her increasing pain and disability.
 
On examination, her weight was 118 lbs, height 5' 4", and BMI 21. Her vital signs were normal. She had swelling and tenderness of her MCPs and PIPs. Although she could make a closed fist, her grip strength was weak. Wrists were swollen, tender, and painful on flexion to 40 degrees. Both extensor carpi ulnaris tendon sheaths were visibly swollen and minimally tender. Her right elbow lacked 10 degrees of full extension; her shoulders were tender and painful on abduction and external rotation to 70 degrees.
 
 Right hip examination revealed decreased internal and external rotation and decreased abduction. Both knees were mildly swollen and painful on flexion beyond 100 degrees. Moderate pes planus was noted. Metatarsal joints were swollen and tender on lateral compression. She had limited flexion of her lumbar spine and a moderate dextroscoliosis.
 
General examination was unremarkable except for an irregular heartbeat and redness at the inner canthi of both eyes. The patient has right groin pain and difficulty with putting on her right stocking, a motion that requires flexion and external rotation of her hip. Her difficulty with entering her car is probably the result of impaired hip abduction. The likelihood of her having right hip disease is high. This joint may be at further risk due to abnormal load bearing as a consequence of her scoliosis.
 
Another diagnostic possibility is avascular necrosis, possibly related to irregular corticosteroid use. If indeed, the right hip has radiologic changes attributable to RA, this would portend more aggressive disease. If avascular necrosis is a serious consideration, MRI would be the diagnostic procedure of choice. Useful
 
This patient has had RA for at least 4 years. Initial disease activity was followed by a more quiescent period during which she had "tolerable" disease.
 
Clearly, a significant percentage of patients with a 4-year history of RA have radiologic changes, ie, periarticular demineralization, joint space narrowing, and/or erosions, which may develop even in the absence of marked pain and swelling. Soft tissue swelling and gross joint damage (eg, subluxation) may be appreciated clinically, but radiographs are needed to assess joint damage, which frequently defies physical examination. Baseline radiographs of hands/wrists and MTP joints may help to determine the efficacy of treatment over time, since the goal of newer disease remitting therapies is the complete arrest of radiologic progression. Very useful
 
Anti-CCP is a highly specific marker for RA. The autoantigenic targets for anti-CCP are citrullinated peptides that contain the epitope recognized in antikeratin, antiperinuclear factor, and antifilaggrin assays. All of these tests are virtually specific for RA, but are technically difficult to standardize. Testing for anti-CCP antibodies is probably most appropriate in patients who are rheumatoid factor seronegative or equivocally positive, but whose clinical picture suggests a diagnosis of RA.
 
Although the specificity of traditional immunoglobulin M rheumatoid factor in RA is around 75% to 80%, the specificity of FDA approved assays for anti-CCP in RA may be as high as 96%. About 40% of seronegative RA patients are likely to be anti-CCP positive. There is some speculation that anti-CCP positivity may be predictive of more erosive disease. Since this patient was RF+, the information that an anti-CCP assay would have provided would be marginally useful. Not useful
 
This woman is currently postmenopausal, has used glucocorticoids over many months, and has an inflammatory polyarthropathy, all of which are independent risk factors for osteoporosis and a future fracture. In addition, her small stature (118 lbs) suggests that peak bone mass may have been low. Generally, a weight of less than 127 lbs predisposes one to osteoporosis. Moreover, the possibility exists that she will need corticosteroids to some degree in her future therapy. A baseline bone density study would help to determine the existence of osteoporosis/osteopenia and the efficacy of prescribed anti-resorptive therapy. Useful
 
On examination, her weight was 118 lbs, height 5' 4", and BMI 21. Her vital signs were normal. She had swelling and tenderness of her MCPs and PIPs.
 
Although she could make a closed fist, her grip strength was weak. Wrists were swollen, tender, and painful on flexion to 40 degrees. Both extensor carpi ulnaris tendon sheaths were visibly swollen and minimally tender. Her right elbow lacked 10 degrees of full extension; her shoulders were tender and painful on abduction and external rotation to 70 degrees.
 
Right hip examination revealed decreased internal and external rotation and decreased abduction. Both knees were mildly swollen and painful on flexion beyond 100 degrees. Moderate pes planus was noted. Metatarsal joints were swollen and tender on lateral compression. She had limited flexion of her lumbar spine and a moderate dextroscoliosis.
 
General examination was unremarkable except for an irregular heartbeat and redness at the inner canthi of both eyes
 
The patient was started on celecoxib 200 mg daily, prednisone 7.5 mg daily, and MTX 15 mg po once weekly. She was told to take acetaminophen 1 gm q8h PRN for break-through pain. In addition she was given a prescription for folic acid 1 mg daily. Since her dietary intake of calcium was less than optimal, she was advised to take supplemental calcium (1,200 mg/day) and vitamin D (800 IU daily).
 
She was given an appointment to return in 3 weeks, but failed to show. Four weeks later, however, she appeared at the clinic for an unscheduled visit (ie, about 7 weeks after her last visit). At this time, she reported a marked increase in stiffness and pain in her hands, which was increased by motion. Her wrists, shoulders, and knees were stiff and painful. Her feet were painful on weight bearing. She had difficulty with grasping small objects and walking more than 50 feet. She was unable to lie on her right side. She stated that she had had a marked improvement in her symptoms shortly after her first clinic visit, to the point where she was even able to work overtime hours.
 
However, after 2 weeks of being compliant with her medications, one of her regular customers told her that prednisone "would deteriorate my bones." She abruptly discontinued this medication. After her 2-week supply of celecoxib samples ran out, she failed to fill her prescription, because she was uncertain as to whether it was "worth the money." She also noted a "gritty" sensation in her eyes. Following this, her symptoms rapidly worsened.
 
Examination revealed multiple swollen and tender PIPs and MCPs. She was unable to make a closed fist. Both wrists were swollen and tender and evoked pain with passive motion. Her right elbow was swollen and tender and had a 20-degree flexion contracture.
 
Both shoulders had pain on abduction, which was intensified by minimal passive external rotation. Right hip findings were unchanged, but there was marked tenderness of the right greater trochanter. Her knees and MTP joints were essentially the same as on her initial visit. Two or three tender nodules in a "crop" were noted at the left olecranon. The "pink eye" noted on her first clinic visit appeared more diffuse.
 
A review of laboratory studies done on her first visit revealed the following:
CBC: normal except for a low-grade normochromic and normocytic anemia
 
Hemoglobin: 11.5 g/DL ;Hematocrit: 33.4% ;ESR: 54 mm/hr
(Westergren) ;CRP: 3X upper limit of normal; RF: positive 320 IU (normal = 0-30) ;ANA: positive 1/80 speckled pattern (not considered significant) ;Metabolic panel: normal except for a borderline albumin of 3.5 g/DL ;Urinalysis: within normal limits
 
Radiographic studies of her hands: narrowing of both radiocarpal articulations and erosions of both ulnar styloid processes. Juxta-articular demineralization involved most joints of both hands. On the right, there was narrowing of the 1st, 2nd, and 3rd MCP joints. A small erosion was present at the base of the 2nd right proximal phalanx. On the left, erosions were also noted at the radial aspects of the 2nd and 4th metacarpal heads. All PIP joints were narrow, but no erosions were noted.
 
Radiographs of her feet revealed "punched out" erosions of the lateral aspects of both 5th metatarsal heads. The 1st right MTP revealed joint space narrowing (JSN). Other changes were minor. Pelvic radiographs revealed uniform loss of cartilage (JSN) of the right hip. No erosions, bone cysts, or protrusion, were present.
 
Given the chronicity of her joint disease, changing NSAIDs is unlikely to alter her clinical status much. The pathologic nature of her synovitis likely has an acute component, which may be affected to some degree by COX inhibition.
 
However, the chronic nature of her illness and the presence of JSN and erosions suggest that her synovitis has evolved into an invading granulation tissue, ie, pannus. The cytokine products of this "aggressive" synovial tissue, which drive the process of joint destruction at the cartilage-pannus junction are not likely to be inhibited by COX inhibition alone. Therefore, whereas NSAIDs may have a significant effect on the synovitis of early RA, their use in later stages is generally less helpful.
 
However, this patient was not compliant in taking her celecoxib on a b.i.d. basis, as prescribed. Switching her to an NSAID given on a once-daily dosing schedule, (eg, piroxicam, oxaprozin, rofecoxib) might offer an advantage in this respect. Somewhat useful
 
This is likely to suppress the inflammatory response more quickly and predictably than any other modality. Not only can one expect relief of pain and stiffness, but more "systemic" problems, such as fatigue, weight loss due to lack of appetite, and "no energy" are likely to be improved. In addition, a rapid change in objective measures of inflammation are likely to be seen, ie, decreases in ESR and CRP and an increase in hemoglobin.
 
The use of local (intra-articular) corticosteroids can predictably decrease the inflammatory process rapidly in specific joints. This may allow the patient to do things she otherwise would be unable to do. Although corticosteroids have many potential adverse effects, the most significant is the loss of bone strength (decreased bone density) in a patient population already at higher risk of fractures. However, the prophylactic use of bisphosphonates has had a dramatic effect on mitigating this problem. Very useful
 
Current standard-of-care RA management calls for rapidly increasing the dose of MTX, if tolerated, to 20 mg to 25 mg weekly. This patient has been tolerating her MTX quite well. If the MTX dose is increased at this point, consideration should be given to administering the drug parenterally to ensure complete bioavailability. Very useful
 
There are data showing that the addition of a second or even third DMARD is likely to yield greater ACR20 and ACR50 responses than MTX used as monotherapy. The addition of HCQ and/or SSZ may be considered in this patient's clinical setting. However, the time lag for each of these medications to become effective, if indeed they do become effective, is likely to be weeks or months.
 
Using more than one standard-of-care DMARD in this case should depend on the physician's assessment of how quickly the pathologic processes must be halted in order to prevent further progression of her already established erosive disease.  Somewhat useful
 
Anti-tumor necrosis factor-alpha (TNF-alpha) therapy and inhibition of the action of IL-1 have been shown to be extremely effective in the management of aggressive RA, both as monotherapy (adalimumab, etanercept, and anakinra), and when combined with MTX (all available biologics). Frequently, the therapeutic response to even a single dose of a TNF-alpha inhibitor is noted within days. Most rheumatologists have seen a more predictable response with the inhibition of TNF-alpha than with down-regulating the effect of interleukin-1 (IL-l) using anakinra.
 
TNF-alpha is the central cytokine that drives the destructive pathohistologic processes seen in RA. It is produced primarily in macrophages and increases the production of IL-l and IL-6, ultimately up-regulating the production of matrix metalloproteases that degrade connective tissue matrix, contributing to the loss of cartilage and bone.
 
TNF inhibition clinically depresses all pathological events leading to joint deterioration, including angiogenesis and osteoclastogenesis. Rheumatologists experienced in the use of these biologic agents have witnessed profound improvement in their patients and are increasingly considering the use of these agents in earlier disease, particularly in patients profiled to be at high risk for joint destruction.
 
These might include patients with multiple joint involvement at the time of presentation, high RF titers, rapid and early functional decline, the presence of erosions in early disease, and the presence of extra-articular features. It should be noted that this patient not only had nodules, but also evidence at her initial visit of a sectoral episcleritis, which later became more diffuse. When patients are properly selected for biologic therapy, TNF inhibitors appear to be quite safe.
 
Some patients do not respond sufficiently to TNF-alpha inhibition, but for those who do, the improvement in quality of life is often dramatic. The percentage of patients who actually achieve a full remission is difficult to assess, but for the most part, the majority of patients derive a degree of benefit unlikely to be obtained with any other treatment modality.
 
The choice of which biologic agent to use is influenced by a number of factors. Occasionally, third party payor reimbursement issues play a role in this decision. For some patients, the ability or desire to self-inject may influence this decision.
 
Some physicians who have used infliximab have observed the phenomenon of "dosage creep." This effect may be diminished by using higher doses of MTX and/or adding a low dose of prednisone. Etanercept and adalimumab presently have suggested fixed doses. Some physicians who have used these medications have the impression that an increase in dose has the potential to yield a greater clinical response in some patients.
 
Although the use of anakinra has not been associated with opportunistic or cardiac complications, most rheumatologists have not seen in this agent the rapid efficacy of TNF-alpha inhibitors. However, those patients who fail TNF-alpha inhibition may respond to anakinra. In addition, the efficacy of anakinra may occasionally increase over time (usually 2-3 months), so that premature discontinuation of anakinra should be avoided if the patient is tolerating the daily subcutaneous injections well. Very useful
 
This patient's compliance to the prescribed medications has been dismal. It is conceivable that she was never really informed about the potential seriousness of her disease. Alternatively, she might be more concerned with possible side effects of medications than with the effects of the disease itself.
 
Clearly, spending some time with her to discuss the nature of RA, the newer targeted therapies, and the need to be compliant might be helpful here. It is important to give her the hope that deformity and disability are not inevitable, and that with rigorous attention to clinical details and the use of these newer, more effective therapies, her quality of life and functional capacity are likely to improve.
 
Switching her to parenteral MTX and requiring her to be seen weekly, at least for a time, might be helpful in monitoring her compliance. This would also allow the nursing staff to play a role in educating her about her illness. Very useful
 
The patient was switched from celecoxib to rofecoxib in order to enhance the likelihood of compliance. She was also restarted on prednisone, 10 mg/day, and was reassured that the lowest effective dose of prednisone would be used with the expectation that it could be discontinued altogether as her disease activity waned. Her MTX dose was increased to 20 mg IM once weekly and was to be given by the clinic nurse, at least initially, to monitor compliance.
 
The decision to use a TNF-alpha inhibitor was also made at this time, since it offered the most predictive response in a rapidly deteriorating clinical situation.
 
 Also, considerable time was spent on educating her about RA.
 
At this clinic visit, her right greater trochanteric bursa was injected with 20 mg of triamcinolone diacetate and lidocaine. In addition, 8 ml of synovial fluid were aspirated from her right shoulder and 15 mg of triamcinolone hexacetonide were instilled.
 
Preparation for using a TNF inhibitor, which of the following studies is likely to be helpful? 
   
Purified Protein Derivative (PPD) skin test: Treatment with anti-TNF-alpha compounds has resulted in the reactivation of latent tuberculosis (TB) and other opportunistic infections, including histoplasmosis and coccidioidomycosis in endemic areas, listeriosis, pneumocystosis, and herpes simplex type II. TNF-alpha plays a significant role in granuloma development and maintenance, allowing Mycobacterium tuberculosis to reside intact and viable for years within macrophages confined in stable granulomata. Inhibition of TNF-alpha has the potential to disrupt this stability, leading to reactivated infection.
 
Tuberculosis associated with TNF-alpha inhibition has often been very virulent, occasionally presenting with disseminated disease, including lymph node involvement. Mortality rates, even with treatment, have been as high as 20%. Very useful
 
Chest x-ray: Pulmonary abnormalities, especially evidence of past granulomatous disease, may well alter the decision to postpone or abandon anti-TNF therapy until the nature of the abnormal findings are established and treated if possible. Very useful
 
The use of anti-TNF therapy in patients with recurrent or chronic urinary tract infections may be contraindicated or require long-term antibacterial suppression. This problem may be particularly applicable in the setting of benign prostatic hypertrophy in men or in women with a cystocele. Useful
 
ECG: TNF-alpha is elaborated by failing myocardial tissue in response to pressure or volume overload. Although increased levels of TNF-alpha are found in plasma samples from patients with congestive heart failure (CHF), the use of anti-TNF therapy in patients with CHF has resulted in worsening of their clinical state. Clearly, patients with Class III or IV CHF are not candidates for TNF-alpha inhibition. Its use in lesser degrees of CHF should be approached cautiously, eg, with lower dosing, if at all. An ECG is unlikely to be helpful in determining the existence of CHF. Not useful
 
The patient returned to the rheumatology clinic 3 days after her PPD, chest x-ray, and urinalysis were done. A chest x-ray revealed the presence of a small right upper lobe density consistent with "old granulomatous disease." Her PPD was strongly positive. Further history obtained from the patient at this time revealed that her father had died in a "sanitarium" while she was a child in Europe. A diagnosis of latent tuberculosis was made. Urinalysis was unremarkable.
 
At this visit, she was given a prescription for isoniazide (INH) 300 mg once daily with the expectation that she would remain on this therapy for 9 months. Liver function tests at appropriate intervals were to be obtained to monitor possible INH toxicity.
 
After starting treatment for latent tuberculosis, what is the earliest you would consider starting anti-TNF therapy? 1 day. Once anti-tuberculosis therapy has been initiated, it is possible to start anti-TNF therapy immediately.
 
This patient was begun on an anti-TNF regimen 1 week after INH was started. Her response, in terms of joint pain, swelling, and stiffness, was dramatic. Even after 2 years of anti-TNF therapy, she has continued to show improvement in various measures of functional assessment. She has returned to work without restrictions and has had no absences due to her RA.

Diagnosis of RA is premature:
 
A 33-year-old woman went to her physician reporting painful fingers and a progressive loss of ability to grip small objects over the last 2 to 3 months. She noted feeling sore when she gets up in the morning. She feels tired all the time. She has been sleeping poorly because she gets uncomfortable at night and needs to get up and walk around several times. To relieve the pain, she has been taking 1 or 2 tablets of over-the-counter ibuprofen 5 times a day. The medication is ineffective.
 
Physical examination showed mild tenderness at the proximal interphalangeal (PIP) and MCP joints of the second through fifth fingers of both hands. There was no swelling or warmth. She had point tenderness along the upper border of the trapezius at her upper back, the posterior superior pelvic brim, the back and sides of her neck, and the elbows near the lateral epicondyles. The patient wears contact lenses and noted that recently she has had a little more trouble with "mattering" on her eyes. She has occasionally used nonprescription eye drops for red eyes over the last 6 months.
 
For this patient, the differential diagnosis includes diseases that can cause inflammatory symmetric arthritis, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), as well as diseases with features that can mimic inflammatory symptoms, including fibromyalgia and hypothyroidism. She has soft tissue tenderness, which is consistent with fibromyalgia, but the prominent hand involvement suggests another process. Joint tenderness, which is the most sensitive sign of inflammation, may be present before swelling and warmth can be appreciated.
 
In pursuit of findings indicative of inflammatory disease, it is advisable to clarify whether the soreness the patient feels when she arises could be considered morning stiffness (i.e., a sense of resistance to movement that improves with use over time). Subtle historic features, such as changes in the ability to get rings on and off, can be helpful clues. Patients should be asked about symptoms of thyroid disease, but, other than rheumatic symptoms, individuals with mild hypothyroidism often have little clinical evidence of thyroid dysfunction.
 
The patient's remarks concerning her eye problems may be relevant. These symptoms should be explored, and she should also be asked whether she has dry mouth, trouble swallowing dry foods, or other oral symptoms. The causes of the patient's sleep disturbances should be pursued. In this case, the questioning revealed that the sleeplessness was starting to affect her mood, although she denied any serious depression. She reported that she has always had trouble with cold intolerance but this had not changed.
 
At this point, the list of possible diagnoses is still fairly long. Sjögren's syndrome is suggested by the eye symptoms. Schirmer paper can be used in the office to measure tear production, and an ophthalmology consultation may be useful for evaluation of possible keratoconjunctivitis sicca.
 
Laboratory tests that are likely to be helpful include the erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), because confirmation of inflammation is very helpful in establishing the correct diagnosis.
 
Because the diagnostic possibilities include early RA, SLE, and Sjögren's syndrome, one should also check rheumatoid factor (RF), ANA, and antibodies to SSA and SSB (Sjögren's syndrome A and B) antigen. Thyroid function should be measured; the most cost-effective test is measurement of thyroid-stimulating hormone (TSH), assuming the laboratory is using a second- or third-generation TSH assay.
 
Treatment could include higher doses of an anti-inflammatory agent as well as low-dose amitriptyline for fibromyalgia. A therapeutic and diagnostic trial of low-dose prednisone might be warranted. Although a rapid response to prednisone is characteristic of inflammatory diseases, some patients with noninflammatory diseases may also feel better while receiving corticosteroids, making interpretation of such therapeutic trials problematic.
 
She was treated with a long-acting prescription nonsteroidal anti-inflammatory drug and amitriptyline 25 mg at night. Laboratory test results revealed a RF positive at 600 IU/mL (a high titer); ANA was positive at 1:80 with a speckled pattern; anti-SSA/Ro was negative. The ESR was 50 mm/hour, and the CRP 3.7 mg/dL, both moderately elevated. CBC revealed a hematocrit of 35%, hemoglobin of 12.2 g/dL, and normal white blood cells (WBC) and platelets. A TSH was within the normal range.
 
On her return to the physician's office 3 weeks later, the patient reported that she was sleeping better but was still diffusely sore in the morning and was still having trouble with her hands. She was having difficulty keeping up with her job, which required a lot of keyboarding, because of pain and stiffness in her joints. She reported neither numbness nor tingling in her fingers.
 
The laboratory tests show that this patient has an inflammatory process. The high positive RF in the face of a low-titer ANA suggests that she has early RA.
 
She also has morning stiffness and fatigue, both of which are associated with inflammatory diseases. It is somewhat surprising that the physical examination did not reveal additional evidence of inflammation, but in some patients the laboratory tests are earlier indicators. She could have early ocular sicca secondary to RA.
 
In order to maintain her job, she needs more aggressive therapy quickly. Low-dose prednisone (10 mg/day or less) is likely to allow her to maintain a reasonable level of function at home and work. Since objective swelling has not been identified, methotrexate is not advisable. Hydroxychloroquine or sulfasalazine are reasonable choices.
 
Prednisone 10 mg every morning and hydroxychloroquine 200 mg twice a day were prescribed. The patient was referred to an ophthalmologist for a baseline exam for following antimalarial treatment and to explore the possibility of keratoconjunctivitis sicca. In anticipation that methotrexate might be needed, baseline hand x-rays were obtained and liver function tests and viral hepatitis antibody panels ordered.
 
The patient reported back that she substantially but incompletely improved within a few days of starting prednisone. Hand x-rays were normal. Liver function tests showed minimal elevations in the transaminases and a normal alkaline phosphatase. The hepatitis B surface antigen was negative; the hepatitis C antibody and hepatitis B surface antigen tests were positive.
 
This patient has been exposed to hepatitis B and C. She could have been immunized with hepatitis B or have previously been infected and recovered from hepatitis B virus infection. About 80% of patients with hepatitis C virus (HCV) are chronically infected. A variety of rheumatic disease symptoms may be seen in some patients with HCV infection.
 
The patient reported that she had a hepatitis B vaccine several years ago. She reported no use of needles for illegal drugs. She had received a blood transfusion in 1988 for postpartum bleeding. She reported no history of jaundice or symptomatic hepatitis.
 
Quantitative tests for HCV RNA showed low levels of HCV in the plasma. The patient was referred to a hepatologist. Her joint symptoms were improving on hydroxychloroquine, and she had been able to taper the prednisone to 5 mg/day.
 
Posttransfusion hepatitis C was relatively common prior to effective screening of blood products for HCV, which began in 1992. Among patients with chronic hepatitis C, approximately 70% have RFs, and significant numbers have positive ANAs. Large numbers of these patients also have mild sicca symptoms and lymphoid infiltrates on salivary gland biopsies. Some have arthritis as well.
 
This patient should be followed to determine whether overt signs of RA and mixed cryoglobulinemia syndrome develop. Effort must be made to ensure that urinalysis and serum creatinine are normal and to look for signs of cutaneous vasculitis when the patient returns. A diagnosis of RA wold be premature, despite the presence of inflammation and a positive test for RF.
 
Laboratory Tests in Context: I) Erythrocyte sedimentation rate and C-reactive protein are nonspecific indices of inflammation.
 
II) Rheumatoid factor (RF) per se is not diagnostic; a positive RF test can result from hepatitis C virus infection.
 
III) The patient history, physical examination, and clinical course, as well as the results of laboratory tests, are needed to establish a diagnosis.