True primary Sjögren's syndrome in a subset of patients with hepatitis C infection: a model linking chronic infection to chronic sialadenitis.
BACKGROUND
Hepatis C virus infection is presently an exclusion criterion to classify Sjögren's syndrome; however, there are distinct clinicopathologic and biologic similarities between HCV-related and SS-related chronic inflammation of mucosa-associated lymphoid tissue and lymphoproliferation that suggest common pathogenetic pathways.


OBJECTIVE
To determine whether a subset of patients with sicca syndrome and HCV infection may present a true primary SS rather than a distinct clinicobiologic entity.


METHODS
We extensively characterized 20 consecutive patients with positive anti-HCV antibodies and heavy subjective dry eye and/or dry mouth symptoms, plus positive unstimulated sialometry and/or Shirmer's test. We then compared these features with those in HCV-negative primary SS controls (classified according to the latest American-European Consensus Group Classification Criteria for SS).


RESULTS
Of the 20 HCV-positive patients with sicca manifestations, 12 (60%) had positive anti-SSA/SSB antibodies (3/12 by enzyme-linked immunosorbent assay and 6/12 by immunoblot) and/or positive salivary gland biopsy (at least 1 focus/4 mm2), which met the strict classification criteria for SS, as in the case of HCV-negative SS controls. Comparing the HCV-positive SS subset with HCV-negative SS controls showed similar female to male ratio (11/1 vs. 46/4), major salivary gland swelling (17% vs. 26%), positive antinuclear antibodies (75 vs. 94%) and positive rheumatoid factor (58 vs. 52%). Significant differences (P < 0.05) were seen in mean age (69 vs. 56 years), liver disease (50 vs. 2%), lung disease (25 vs. 0%), anti-SSA/SSB positivity (25 vs. 90%), and low C3 or C4 (83 vs. 36%). HCV-positive SS patients exhibited a trend for more frequent chronic gastritis (50 vs. 22%), fibromyalgia (33 vs. 14%), peripheral neuropathy (33 vs. 18%), purpura (33 vs. 19%) and cryoglobulinemia (33 vs. 6%).


CONCLUSIONS
A major subset of HCV-positive patients with definite subjective sicca symptoms and positive objective tests may indeed present a true, though peculiar, subset of SS. There are strict similarities with key clinical, pathologic and immunologic findings of definite HCV-negative SS. Other features appear more characteristic of HCV infection. When also considering that HCV is sialotropic and may be treated, HCV-related chronic sialadenitis represents a unique opportunity to clarify key pathogenetic events occurring in the large majority of HCV-negative SS; and similarities to typical primary SS, rather than differences, should be taken into account.
De Vita
Salvatore
S
Department of Rheumatology, DPMSC, University of Udine, Udine, Italy. salvatore.devita@med.uniud.it
Damato
Rosaria
R
De Marchi
Ginevra
G
Sacco
Stefania
S
Ferraccioli
Gianfranco
G
D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000032:analysis; D001706:Biopsy; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000032:analysis; D012469:Salivary Glands / Q000473:pathology; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D018709:Statistics, Nonparametric
D000974:Antibodies, Antinuclear; D012217:Rheumatoid Factor