Hepatitis C Virus-related Arthritis: Bone Scintigraphic Appearances

Introduction

The rheumatologic manifestations associated with hepatitis C virus (HCV) infection include arthralgia, myalgia, arthritis, vasculitis, and sicca syndrome.[1234567891011] Arthralgia is relatively common in HCV, but arthritis is not.[12345678] Scintigraphic findings in hepatitis-related arthritis have not been previously reported. We presented a patient with areas of joint pain that corresponded to the regions of increased Tc-99 m methylene diphosphonate (MDP) uptake. This demonstrates the ability of bone scan to image symptomatic joint, suggesting its potential value in the early diagnosis when compared radiography.

Case Report

We present a case of a 63-year-old male with chronic hepatitis C, who presented with bilateral symmetrical painful joints including hands, wrists, elbows, and shoulders in the upper limbs. There was no pain in low extremity joints. In addition, he described stiffness in the regions of the right shoulders joints and swelling in the right wrist and hand regions. A small cell lung cancer diagnosis was also made 2 months ago.

Laboratory findings showed elevated levels of rheumatoid factor (RF) and normal level anti-cyclic citrullinated peptides (CCPs) antibodies. The radiography of the upper and lower limbs did not show any abnormality [Figure 1]. However, the result of a subsequent bone scan including three phase of upper extremities and whole body were grossly abnormal. The images of the whole body [Figure 2], blood pool, and delayed uptake [Figure 3] showed multiple areas of intense increased MDP uptake in the bilateral interphalangeal and metacarpophalangeal joints of hands, wrist, elbow, and shoulders and less intense increased uptake in the foot joints. There was an excellent correlation between the areas of arthritic pain and the regions of increased uptake.

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Figure 1 Normal plain radiography of both painful hands

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Figure 2 Anterior (a) and posterior (b) whole body bone scan demonstrated a largely symmetric polyarthropathy affecting large and small joints in the upper and lower limbs. Note the diffusely increased uptake with a parallel track pattern of hypertrophic pulmonary osteoarthropathic in the femurs and tibiae

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Figure 3 On bone scan of both hands, there is increased blood pool activity (a) and delayed uptake (b) in the areas of the joint involved

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In addition, in whole body scan, there was hypertrophic pulmonary osteoarthropathic appearance (affecting femora and tibiae). The increased osteoblastic activity in the region of thoracic vertebras was determined to be spinal bone/mainly bone-marrow metastases secondary to lung carcinoma by magnetic resonance imaging.

Discussion

Several viruses have been associated with the development of inflammatory arthritis including hepatitis viruses (hepatitis B virus [HBV] and HCV), HIV, parvovirus B19, human T-cell lymphotropic virus-I, and alphaviruses.[9101112]

Arthralgias, reported in 20–83% of HCV patients, are bilateral, symmetric, nondeforming and mainly involve knees and hands, more seldom elbows, and ankles.[12345678] The prevalence of arthritis ranged across studies from 4% to 11%. HCV infection-related arthritis (HCVrA) is usually distinguished in two clinical subsets: A more frequent symmetrical polyarthritis in which 50–85% of patients are RF-positive, similar to rheumatoid arthritis (RA) but less serious, and mostly intermittent mono- and oligoarthritis that involves medium and large sized joints, mainly the ankle.[12345678] The arthropathy is nonerosive/nondeforming, and no joint erosions are seen on radiographs. In 50–80% of cases, RF is positive. An important point in distinguishing RA from HCVrA is given by the presence of anti-CCP antibodies.[468] There are several pathogenic mechanisms by which HCV may induce arthritis.[12345678] The most extensively studied mechanism underlying HCVrA is HCV mixed cryoglobulinemia. Other possible mechanisms include direct invasion of synovial cells by the virus, eliciting a local inflammatory response, cytokine-induced disease (other than cryoglobulinemia) associated with chronic, persistent HCV infection, or other mechanisms associated with reactive arthritis.

Bone scanning has been used in various forms of arthritis. An increased uptake occurs before radiographic changes are evident, which allows a more accurate estimate of disease extent and may indicate involvement in joints that are as yet asymptomatic. Pathologic features of arthropathies have been translated into various patterns of findings on scintigraphic imaging modalities.[13] The pattern of symmetric peripheral joint involvement of RA can usually be distinguished scintigraphically from that of the rheumatoid variants (ankylosing spondylitis, psoriasis, Reiter's syndrome, etc.), which tend to have more central skeletal involvement and asymmetric peripheral articular uptake.

We described a patient (with normal plain radiography) whose areas of arthritic pain exactly matched the regions of increased MDP uptake. Painful upper limbs joints demonstrated intense increased uptake, whereas as painless foot joints showed less increased uptake.

Accurate and early diagnosis of HCVrA is important so as to avoid immunosuppressive therapy, which likely may be ineffective in managing arthritis, exacerbate the viral disease, and delay effective palliative antiviral treatment.[467] Because these patients often present with confusing clinical features, there usually is a delay in the diagnosis of HCV infection, leading to a prolonged period of unsuccessful therapeutic trials. Although this arthritis may be difficult to distinguish from other common chronic arthropathies, most notably RA, it is important to consider this arthropathy in the differential diagnosis of every newly presenting oligo- or polyarthritis.[4] The patient was also tested for some other causes of polyarthritis; HBV, HIV, and lupus psoriasis at the time of further diagnosis, and the laboratory findings were negative. Because of significant differences in treatment strategies between RA and HCV arthropathy, future research efforts should focus on clarifying diagnostic differences between HCVrA and other arthropathies.[467] In larger patient groups with HCVrA and other virus-related arthritis,[9101112] further studies are needed both to assess scintigraphic uptake patterns for distinguishing than other arthropathies and to evaluate treatment response.