Hepatitis C virus infection in psoriatic arthritis

Authors


Abstract

Objective

To evaluate the prevalence of hepatitis C virus (HCV) infection in patients with psoriatic arthritis (PsA), compared with patients affected by non HCV-related rheumatic degenerative disorders.

Methods

One-hundred consecutive subjects with PsA, and a statistically comparable group of 100 consecutive patients with peripheral osteoarthritis (OA) or sciatica due to L4–L5 or L5–S1 herniated disc were tested for HCV infection with a third-generation microparticle enzyme immunoassay (MEIA). Positive cases were submitted to a third-generation recombinant immunoblot assay (RIBA) confirmatory test. Comparison between the HCV prevalence obtained in the 2 enrolled groups was performed using Fisher's exact test.

Results

Anti-HCV antibodies were found with the MEIA method, in 1 patient with PsA, and in 4 patients with OA or sciatica. The RIBA method confirmed MEIA results in all positive patients. The difference in HCV prevalence detected in the PsA group and in the control group was not statistically significant (P = 0.68). Furthermore, HCV prevalence in PsA patients was lower than the ones reported in different geographic areas of Italy.

Conclusion

Our present report does not confirm previous data that indicated an increased prevalence of HCV in PsA patients, and as a consequence, does not sustain a possible trigger role of HCV in cases of PsA. The absence of clinical or instrumental resources that consent a definite differential diagnosis between PsA and HCV-related arthritis was outlined and analyzed.

INTRODUCTION

Joint involvement as arthralgia or arthritis is common in patients with hepatitis C virus (HCV) infection (1–4). HCV-related arthritis can present in 2 subsets: a symmetric rheumatoid arthritis (RA)-like form involving mainly small joints, and a less frequent intermittent monooligoarthritis, involving medium and large joints; the latter is often associated with the detection of cryoglobulins in serum (5, 6). This topic has been recently examined in 2 extended reviews (7, 8). In recent years, some authors reported an increased prevalence of HCV infection in subjects with cutaneous psoriasis (9, 10), but other researchers did not confirm these data (11).

In 1999, Taglione et al reported a high prevalence of HCV infection in 50 Italian subjects with psoriatic arthritis (PsA), compared with subjects with RA and with the general population (12). On the contrary, in the same work, the prevalence of HCV infection in patients with cutaneous psoriasis is not significantly higher than in the general population.

In the present study, we compared the prevalence of HCV infection in subjects with PsA and in subjects with non HCV–related rheumatic degenerative disorders (osteoarthritis and lumbar-disc hernia–related sciatica), all located in the central part of Italy.

SUBJECTS AND METHODS

One-hundred consecutive subjects with PsA were enrolled from February to December, 2002. PsA was diagnosed in patients with inflammatory joint involvement associated with cutaneous and/or nail psoriasis. All suspect skin/nail lesions were examined by a dermatologist. Subjects with other spondylarthritides, RA, crystal-induced arthritis, and connective tissue diseases were excluded. According to the findings of Gladman et al (13), seropositivity alone for rheumatoid factor (RF) was not an exclusion criterion for the diagnosis of PsA. In patients with RF-positive arthritis and psoriasis, definite PsA was diagnosed in the presence of one or more of the following signs: asymmetric involvement, dactylitis, spondylitis, sacroiliitis, chest wall involvement, typical enthesopathy, and typical radiologic PsA findings (14). Patients with RF-positive symmetric polyarthritis without these signs were also enrolled, but in a separate group, and indicated as possible PsA, because a fortuitous association between RA and cutaneous psoriasis cannot be excluded (15). The 100 cases of definite PsA were classified in 5 subgroups, as indicated by Moll and Wright (16). Forty-one patients showed polyarticular and symmetric RA-like involvement, 36 were affected by oligoarthritis, 15 had spondylitis, 7 demonstrated the distal interphalangeal arthritis of the classical subset, and only 1 had distal mutilans involvement of fingers and toes. Mean ± SD age of PsA patients was 56.4 ± 14 years. A group of 100 consecutive patients with from peripheral osteoarthritis (OA) or sciatica due to L4–L5 or L5–S1 herniated disc (two HCV unrelated disorders), was enrolled as controls. Lumbar disc hernias were identified by magnetic resonance imaging. The mean ± SD age of this second group was 55.6 ± 13 years. The difference between mean age of the PsA group and control group was not statistically significant (P = 0.7). In the same period, possible PsA was diagnosed in 3 patients (2 women, 1 man) presenting with symmetric polyarthritis, positive RF, and cutaneous psoriasis, in whom a discriminative diagnosis between PsA and RA was impossible.

In all patients with PsA and control subjects, HCV infection was searched for with a third-generation microparticle enzyme immunoassay test (MEIA) (Abbott Diagnostics Division, Wiesbaden, Germany) and confirmed, in positive cases, by a third-generation recombinant immunoblot assay (RIBA) (Ortho Diagnostic Systems, Raritan, NJ). Other laboratory investigations included erythrocyte sedimentation rate, C-reactive protein, blood cells count, renal and liver function, serum uric acid, serum calcium, serum protein electrophoresis, RF (nephelometric method), Waaler-Rose reaction, HBV antibodies, antinuclear antibodies, antistreptolysin-O antibodies, and urinalysis. Cryoglobulins were searched for in sera of subjects who were HCV positive. All tests were also performed in the patients with possible PsA. Statistical analysis was performed using Fisher's exact test to compare the PsA group and the control group.

RESULTS

Anti-HCV antibodies were found, with MEIA method, in 1 (of 100) patient with PsA and in 4 (of 100) subjects with OA or sciatica. The RIBA method confirmed MEIA results in all positive patients. The difference in HCV prevalence detected in the PsA group and in the control group was not statistically significant (P = 0.68). This result was expected considering the small number of HCV-positive patients in the 2 groups compared.

Type III cryoglobulinemia was found in the HCV-positive PsA patient and the 2 HCV-positive control subjects. The PsA patient with HCV infection had been classified in the symmetric polyarthritis subgroup, as indicated by Moll and Wright (16). None of the 3 subjects with possible PsA had HCV antibodies.

DISCUSSION

At the present time 2 patterns of HCV-related arthritis have been described. The first one can perfectly mimic the clinical picture of RA, while the second consists in intermittent monooligoarthritis, frequently associated with the presence of cryoglobulins in serum (5–8). Two published reports show erosions in 20–30% of subjects belonging to the RA-like subset (5, 17). In these cases, a coexistence of HCV infection and true RA cannot be excluded.

In 1999, Taglione and coworkers found a high prevalence (12%) of HCV infection in 50 Italian patients with PsA (12). This result could lead to hypothesize HCV as the triggering agent of some PsA cases. In effect, a possible pathogenetic role of different microorganisms such as human immunodeficiency virus, streptococci, and enterobacteria have been suggested in PsA (18–20). Discordant results on increased prevalence of HCV antibodies in subjects with cutaneous psoriasis have been previously reported (9–11).

In the present study, we show a very low frequency (1 of 100) of HCV infection in a group of 100 consecutive subjects with PsA. This percentage is lower than the ones reported in the Italian general population (see below). Our data do not sustain the hypothesis of the existence of some relationship between HCV and PsA, for example, a trigger role played by the virus.

Among the 6 cases with PsA and HCV infection described by Taglione et al (12) only 1 had axial involvement, while 1 had oligoarthritis and 4 a polyarticular pattern. Therefore, the chance inclusion of subjects with HCV infection-related arthritis among patients with PsA cannot be ruled out.

In effect, if the differential diagnosis between RA and HCV-related arthritis could be simplified by the detection of antikeratin antibodies (21) or anticyclic citrullinated peptide antibodies (22) that are more frequent in RA, differentiation between PsA and HCV-related arthritis can be problematic. In patients with arthritis with coexisting HCV infection and cutaneous psoriasis, the difficulty in diagnosis is increased when signs such as dactylitis, spondylitis, chest wall involvement, enthesopathy, and other clinical or radiologic findings typical for PsA are absent (14).

HCV-related arthritis is often associated with positive RF (5–8, 23), but the latter can be detected in PsA (15), and also in the normal population. Furthermore, the presence of RF is a frequent sign of HCV infection (24) and can be independent from the articular manifestations. The finding of type II or type III cryoglobulinemia, never reported in association with PsA, could possibly support the diagnosis of HCV-related arthritis, especially in patients with intermittent monooligoarticular involvement; unfortunately this result can also be a simple sign of HCV infection (25).

Obviously, in countries such as Italy, where PsA arthritis is not an uncommon disorder, the risk of misdiagnosis is increased (15). Furthermore, in Italy, the detection of HCV infection is also high in the general population. In effect, the more recent data concerning different geographic areas of this country indicate a prevalence of HCV infection in adults varying from 3.2% to 24.6% (26–30).

MICA-A 9 polymorphism has been found significantly higher in patients with PsA and it was over-represented in the symmetric polyarthritis subset (31). This observation could open the way to better differentiating PsA from other inflammatory joint diseases. At the present time, diagnostic difficulties between both patterns of HCV-related arthritis (polyarticular RA-like and monooligoarticular with intermittent course) and PsA persist, in spite of the use of modern means of investigation. In conclusion, our data do not confirm previous findings that indicated an increased prevalence of HCV in PsA patients, and, as a consequence, do not sustain a possible trigger role of HCV in cases of PsA. The coexistence of psoriasis and HCV infection in patients with arthritis can represent a diagnostic challenge for the clinicians because differentiating criteria and procedures are lacking.

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