Case Report/Clinical Techniques

Vasculitis of Dental Pulp Associated with Cryoglobulinemia in Hepatitis C Virus Patients: Case Report
Mohammed El-Awady Grawish, PhD,* Ahmed Ragheb Zaher, PhD,* Heba M. Elsabaa, PhD,* and Doha Hegazy, PhD†
Introduction: This report presents a case of impacted lower third molar extracted for surgical reasons in patient with uncontrolled hepatitis C. After decalcification, dental pulp vasculature and its tissue quality were investigated. Methods: Serial sections of 4-mm thickness along the midline buccolingually for the demineralized specimen were obtained, mounted on a glass slide, stained with hematoxylin-eosin, covered, and viewed under the light microscope. Results: The histologic investigation of the pulp tissue revealed thickening, stenosis, and occlusion of the vessel wall, ectopic calcification of the pulp tissue in close association with pulpal blood vessels, interrupted and vacuolated odontoblastic layer in the coronal pulp chamber, with an inflammatory cell infiltrate throughout the pulpal tissue. Conclusions: Cryoglobulinemia associated with uncontrolled hepatitis C virus infection in patients endangers the dental pulp vasculature and alters its normal tissue architecture. (J Endod 2011;:1–3)


Key Words
Cryoglobulinemia, dental pulp vasculature, hematoxylin and eosin, hepatitis C virus

From the *Oral Biology Department, Faculty of Dentistry, Mansoura University, Mansoura, Dakahlia, Egypt; and † Hepatology Research Group, Peninsula College of Medicine and Dentistry, University of Plymouth, Plymouth, United Kingdom. Address requests for reprints to Dr Mohammed El-Awady Grawish, Oral Biology Department, Faculty of Dentistry, Mansoura University, Miet El Amel, Aga, Mansoura, Dakahlia 35516, Egypt. E-mail address: 0099-2399/$ - see front matter Copyright ª 2011 American Association of Endodontists. doi:10.1016/j.joen.2011.06.033

gypt has the highest prevalence of hepatitis C virus (HCV) infection of any country in the world. It is estimated to be 8% in urban and 25% in rural areas, with 8–10 million inhabitants having HCV antibodies (anti-HCV) and 5–7 million having active infections (1). The HCV is a small ($55–65 nm), spherical, enveloped, hepatotropic single-stranded RNA positive strand that causes acute and chronic hepatitis in humans. Persistent virus infection with HCV often leads to cirrhosis and hepatocellular carcinoma. At present there is neither a selective antiviral therapy nor a preventive vaccine (2). Patients who are chronically infected with HCV often develop mixed cryoglobulinemia (MC), a B-cell proliferative disorder with polyclonal activation and autoantibody production (3). The syndrome of MC represents the consequence of an immune complex–type vasculitis. It is characterized by the clinical triad of purpura, arthralgia, and asthenia and might involve numerous organs, particularly the peripheral nervous system and the kidneys (4). HCV-related systemic vasculitis might occur in the absence of detectable MC. The findings of Terrier et al (5) suggested that such vasculitis probably results from immune-mediated mechanisms, and that the therapeutic management of such vasculitis should be similar to that of HCV-MC vasculitis. During the past decade, many case reports (Table 1) exist demonstrating that infection with HCV is involved in the pathogenesis of most MC vasculitis. To date, there have been no reports in the literature of HCV-associated cryoglobulinemia effects on dental pulp vasculature and on its tissue quality in patients with uncontrolled disease. Thus, the purpose of this report was to present 1 case in which HCV was a major cause of cryoglobulinemia and to discuss the effects of vasculitis on dental pulp tissue quality. Translation of biological knowledge into the clinical setting can simply involve the adoption of a more biological frame of mind during treatment planning, with the knowledge that the overall response of the tooth to injury represents the complex interplay between injury, defense, and regenerative processes. The balance of all of these events will impact significantly on the opportunity and nature of any regenerative processes within the dental pulp tissue (14).

Case Report
A 30-year-old man was referred to the Department of Oral Surgery, Faculty of Dentistry, Mansoura University by his dental practitioner with a complaint of bone pain and diagnosis of impacted lower third molar. The patient had chronic HCV with no history of regular medical control of the disease and was free from any other medical problems. The HCV-RNA serum level (Amphcor HCV Monitor; Roche Molecular System, Basel, Switzerland) was 1.4 Â 106 genomes/mL, liver enzyme tests showed an increase of alanine aminotransferase serum levels (72 IU/L; normal value, <45 IU/mL), and immunoglobulin (Ig) M with rheumatoid factor activity is found in cryoprecipitates. Radiographic investigations showed that the impacted tooth needed surgical removal. After the impacted tooth was removed, the root apical thirds of the extracted tooth were removed and discarded. Then the tooth was fixed in 10% neutral-buffered formalin for 3 days and kept in 0.5 mol/L ethylenediaminetetraacetic acid (Merck 8417, Darmstadt, Germany) for 20 days for demineralization. Specimen was sectioned longitudinally along the midline buccolingually; both halves were dehydrated and embedded in paraffin. Serial sections of 4-mm thickness were obtained by using a rotary microtome.

JOE — Volume -, Number -, - 2011

Vasculitis of Dental Pulp Associated with Cryoglobulinemia in HCV Patients


The pathophysiologic basis for the HCV-related complications is thought to be immunologic. original magnification. resulting in clinical manifestations. and the long-term chronic infection seems to be the main risk factor for the histopathologic alterations. 2 Grawish et al. 200Â).2011 . . stained with hematoxylin-eosin. Figure 1. Vital pulp therapy performed timely and with effective biocompatible pulp-capping materials as an alternative to routine endodontic treatment contributes to the successful healing and protection of pulp vitality (16). and complement. Number -. Altered dental pulp tissue quality might be attributed to cryoglobulins that had been precipitated within the microvasculature and led to tissue blood flow restriction and tissue hypoxia. stenosis. Our findings Figure 2. Discussion Treatment planning involves appropriately selecting cases. who reported that MC is a systemic vasculitis characterized by the deposition of circulating immunocomplexes in small and medium-sized blood vessels. The deposition of cryoglobulin might act as inflammatory mediator and induce immune-mediated reaction. Photomicrograph of coronal pulp tissue (A) and radicular pulp tissue (B) showing thickening. It is known that HCV-induced MC leads to systemic vasculititis.Case Report/Clinical Techniques TABLE 1. are in accordance with Galossi et al (19). determining how difficult the treatment might be to perform on a specific individual. HCV plays an important role in the development of MC. original magnification. This explanation is in compliance with Ramos-Casals et al (21). and occlusion of vessel wall (BV). lymphoproliferative disorder. and sequencing treatment procedures to achieve a healthy and functional dentition (15). mainly cryoglobulins. with the possible contribution of both hemorheological and local factors. Infection with HCV mainly affects the liver. Ferri et al (20) reported that cryoglobulinemic vasculitis is caused by vascular deposition of circulating immune complexes. disorganized pulpal tissue with inflammatory cell infiltrate (DC) (hematoxylin-eosin stain. interrupted and vacuolated odontoblastic layer in the coronal pulp chamber. JOE — Volume -. with inflammatory cell infiltrate throughout pulpal tissue (Figs. who stated that cryoglobulinemia leads to systemic vasculitis because of inflammation of the vessel walls induced by the deposition of IgM-IgG complexes and subsequent complement activation or causes an ischemic phenomenon because of a direct obstruction of vessels. but it has extrahepatic manifestations. Photomicrograph at area of dentin-pulp complex showing disorganization of pulp tissue with inflammatory cell infiltrate throughout the pulpal tissue (hematoxylin-eosin stain. 100Â). These findings might be attributed to the cryoglobulins that precipitated inside the walls of pulpal blood vessels. and occlusion of the vessel wall. stenosis. renal syndrome. covered. The status of the pulp at the time of capping is the predominant factor in determining the healing of exposed pulps (17). The pathologic investigation of this case reported thickening. ectopic calcification of pulp tissue in close association with pulpal blood vessels (EC). The purpose of this report was to describe the histopathologic alterations of the dental pulp in a patient with uncontrolled hepatitis C and to alert clinicians to determine the type of pulp therapy for those patients. and viewed under light microscope. 1 and 2). The patient in this study did not have a history of regular HCV treatment. interrupted and vacuolated odontoblastic layer (O). the cryoproteins have large molecular weight and increase blood viscosity. and diabetes (18). which might directly precipitate and induce thrombosis in small vessels of some tissues including the dental pulp. ectopic calcification of the pulp tissue in close association with pulpal blood vessels. Representative Case Reports in Past Decade Describing the Effects of HCV-associated Cryoglobulinemia on Different Tissues and Organs Blood vessels Renal Erythema induratum or nodular vasculitis (6) Polyarteritis nodosa (7) Vasculitis complicated with membranous proliferative glomerulonephritis (8) Polyarteritis nodosa and cryoglobulinemic glomerulonephritis (9) Cutaneous vasculitis (10) Palpable purpura (11) Systemic lupus erythematosus (12) Cerebral vasculitis (13) Skin Systemic Central nervous system The thin slices were then mounted on a glass slide.

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