A 75-year-old woman was hospitalized for fatigue and a biological inflammatory syndrome. Her medical history included hepatitis C virus infection discovered six months prior to hospitalization, the means of transmission of which were not clearly apparent. Patient questioning revealed a severe weariness, diffuse polyarthralgia, a typical case of Raynaud's syndrome and a high level of buccal and ocular dryness dating back over three months. Clinical examination revealed the presence of skin lesions forming round, slightly atrophic yellowish plaques present symmetrically on the forehead and which were completely asymptomatic. Examination of other skin areas was normal. Raynaud's phenomenon was confirmed using cold treatment which brought on a loss of colour in all fingers, and a positive Schirmer test confirmed the ocular dryness. The remaining somatic examination was normal.

Cutaneous sarcoidosis, Sjögren's syndrome and autoimmune thyroiditis associated with hepatitis C virus infection

Laboratory analyses revealed positive antinuclear antibodies (ANA) (x 1,000), positive anti-ds-DNA antibodies (crithidiae luciliae + 1/40), positive anti-SSA and anti-SSB antibodies, positive anti-thyroglobulin antibodies (660 UI) and anti-thyroperoxidases (130 UI). Latex and Waaler-Rose reactions were positive (1,280 UI/ml). Erythrocyte sedimentation rate was 67 and 100 mm and an overall hypergammaglobulinemia was detected based on serum protein electrophoresis. Anti-Sm, Anti-RNP and Anti-Scl 70 antibodies were negative. The ELISA test (2° generation) and the hepatitis C polymerase chain reaction tests were positive. Liver function tests showed only moderate elevation of transaminases. A liver biopsy was not performed in light of the advanced age of the patient, and as there was no apparent need for treatment. The thyroid function (TSH,T3,T4) was normal and an assay for cryoglobulins was negative. The biopsy of the accessory salivary glands revealed a moderate, non-specific, mononucleated, lymphoplasmocytic infiltration compatible with Sjögren's syndrome without sarcoid granuloma.

Renal function, serum ACE values, chest X-ray, hand X-ray, and a mediastinal scan were normal. A biopsy specimen of a cutaneous lesion revealed typical sarcoid granuloma (focal infiltration of epithelioid and giant cells, without caseating necrosis, and negative PAS and Ziehl stains)  Direct immunofluorescence skin examination was negative.

Comments

A few months after HVC infection, the patient presented a cutaneous sarcoidosis, without involvement of internal organs, associated with Sjögren's syndrome and autoimmune thyroiditis. The presence of Sjögren's syndrome was unquestionable as 4 European diagnostic criteria were observed: ocular dryness dating back over 3 months, a feeling of dryness in the mouth dating back over 3 months, Schirmer test results lower than 5 mm in 5 min and positive anti-SSA and anti-SSB antibody tests. Conversely, based on the criteria of the ARA (American Rheumatism Association), the diagnosis of systemic lupus erythematosis could not be made.

The combination of cutaneous sarcoid nodules and HVC is exceptional since only one such case has been reported and would appear to have been induced by interferon-alpha therapy [1].

The association of HVC with autoimmune thyroiditis has been widely reported [2-5], as has the association of HVC with Sjögren's syndrome [2, 3, 6-8] and autoimmune thyroiditis with Sjögren's syndrome [9, 10]. To our knowledge, however, the coexistence of these three diseases has not previously been described. Furthermore, the appearance in the present case of cutaneous sarcoidosis lesions in conjunction with a number of positive autoantibodies seems very uncommon.

Autoimmune disorders have also been described in conjunction with hepatitis C virus infection [2, 3, 11], sarcoidosis [12] or Sjögren's syndrome [9, 10]. In the present case, the association of these three conditions, along with the presence of numerous positive autoantibodies, may not be fortuitous and could be linked to a complex immunological mechanism.