Nodular Scleroderma in a Patient With Chronic Hepatitis C Virus Infection: A Coexistent or Causal Infection?
Nodular scleroderma is a rare form of scleroderma that may occur systemically or locally. The pathogenesis of this variant is unknown. We report the case of a 63-year-old woman with systemic scleroderma and chronic hepatitis C virus (HCV) infection who had numerous papules and nodules on the neck and trunk. Skin biopsies from her lesions revealed characteristic findings of scleroderma. This case not only depicts the rare entity of nodular scleroderma but demonstrates the association of HCV infection with systemic autoimmune diseases such as scleroderma.
Practice Points
- Nodular scleroderma is a rare form of cutaneous scleroderma that can occur in association with systemic scleroderma or localized morphea.
- The clinical features are characterized by solitary or multiple, firm, long-lasting papules or nodules on the neck, upper trunk, and proximal extremities.
- The pathogenesis is still unclear. Some reports have suggested that matricellular protein and growth factor, acid-fast bacteria, organic solvents, or the hepatitis C virus may be involved.
In the case of our patient, papulonodular lesions developed 1 year after the diagnosis of SSc was made, and the histopathologic examination revealed classic findings of scleroderma. As a result, our patient is most appropriately classified as having nodular scleroderma.
Clinical Features
Nodular scleroderma mostly affects young and middle-aged women and is clinically characterized by solitary or multiple firm, long-lasting papules or nodules on the upper trunk and chest, neck, and proximal extremities.1-4,6
Etiology and Pathogenesis
The triggers and cellular mechanisms of nodular scleroderma are unclear. Some authors have implicated matricellular protein and growth factors such as tenascin, connective tissue growth factor, and epidermal growth factor in nodule formation.7,8,11 Yamamoto et al9 cited chemical exposure to a silica-containing abrasive as the cause of nodular scleroderma in a worker.
Possible HCV Association
Some reports have indicated an association between nodular scleroderma and pathogens such as acid-fast bacteria10 and HCV.6 Of note, many extrahepatic conditions have been associated with HCV infection, such as membranoproliferative glomerulonephritis, cutaneous vasculitis, lichen planus, and porphyria cutanea tarda.14
The association of HCV infection with systemic autoimmune disease (SAD) has been described in a number of instances; cryoglobulinemia has most commonly been linked to HCV.15 Although the association between HCV and other SADs is less clear, there is growing interest in a possible relationship between them. To that end, physicians of the HISPAMEC (Hispanoamerican Study Group of Autoimmune Manifestations Associated With Hepatitis C Virus) study group described the clinical and immunologic characteristics of 1020 patients with SAD and associated chronic HCV infection. The 3 most frequent SADs (>90% of cases) were Sjögren syndrome, rheumatoid arthritis, and systemic lupus erythematosus.16 However, the strength of association differs for each SAD based on existing descriptions.16,17 Less commonly, there may be a causal relationship between HCV infection and SSc. It should be noted that most of these data are based on small series and case reports.6,16-19
The role of HCV in the pathogenesis of systemic scleroderma and other autoimmune diseases is unknown. It is also possible that the replication of HCV outside the liver, particularly in mononuclear cells, may suppress immune tolerance in genetically predisposed individuals.20
Conclusion
Nodular scleroderma associated with HCV infection is a rare entity. At present, it cannot be determined whether there is an etiopathologic association between HCV infection and SSc or whether the simultaneous diagnosis may be coincidental. Routine determination of HCV serology in scleroderma patients may help to clarify this issue.
