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Vasculitis of Dental Pulp Associated with Cryoglobulinemiain Hepatitis C Virus Patients: Case Report Mohammed El-Awady Grawish, PhD,*  Ahmed Ragheb Zaher, PhD,*  Heba M. Elsabaa, PhD,* 

and Doha Hegazy, PhD † 

 Abstract

Introduction: This report presents a case of impactedlower third molar extracted for surgical reasons inpatient with uncontrolled hepatitis C. After decalcifica-tion, dental pulp vasculature and its tissue qualitywere investigated. Methods: Serial sections of 4-mmthickness along the midline buccolingually for the dem-ineralized specimen were obtained, mounted on a glassslide, stained with hematoxylin-eosin, covered, andviewed under the light microscope. Results: The histo-

logic investigation of the pulp tissue revealed thick-ening, stenosis, and occlusion of the vessel wall,ectopic calcification of the pulp tissue in close associa-tion with pulpal blood vessels, interrupted and vacuo-lated odontoblastic layer in the coronal pulp chamber,with an inflammatory cell infiltrate throughout thepulpal tissue. Conclusions: Cryoglobulinemia associ-ated with uncontrolled hepatitis C virus infection inpatients endangers the dental pulp vasculature andalters its normal tissue architecture. (J Endod 2011;-

:1–3)

Key Words

Cryoglobulinemia, dental pulp vasculature, hematoxylinand eosin, hepatitis C virus

Egypt 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 activeinfections (1). The HCV is a small ($55–65 nm), spherical, enveloped, hepatotropicsingle-stranded RNA positive strand that causes acute and chronic hepatitis in hu-mans. Persistent virus infection with HCV often leads to cirrhosis and hepatocellularcarcinoma. At present there is neither a selective antiviral therapy nor a preventive vaccine (2).

Patients who are chronically infected with HCV often develop mixed cryoglobuli-

nemia (MC), a B-cell proliferative disorder with polyclonal activation and autoantibody production (3). The syndrome of MC represents the consequence of an immunecomplex–type vasculitis. It is characterized by the clinical triad of purpura, arthralgia,and asthenia and might involve numerous organs, particularly the peripheral nervoussystem and the kidneys (4). HCV-related systemic vasculitis might occur in the absenceof detectable MC.The findings of Terrier et al (5) suggested thatsuchvasculitis 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, therehave been no reports in the literature of HCV-associated cryoglobulinemia effects ondental 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 tissuequality.

Translation of biological knowledge into the clinical setting can simply involve theadoptionof a more biological frame of mind during treatmentplanning, with theknowl-edge 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 bonepain and diagnosis of impacted lower third molar. The patient had chronic HCV with

no history of regular medical control of the disease andwas free from any other medical problems. The HCV-RNA serum level(AmphcorHCV Monitor;Roche Molecular System,Basel, Switzerland) was 1.4Â 106 genomes/mL, liver enzyme tests showed an increaseof alanine aminotransferase serum levels (72 IU/L; normal value, <45 IU/mL), andimmunoglobulin (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 wereremoved and discarded. Then the tooth was fixed in 10% neutral-buffered formalin for3 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 inparaffin. Serial sections of 4-mm thickness were obtained by using a rotary microtome.

From the *Oral Biology Department, Faculty of Dentistry,Mansoura University, Mansoura, Dakahlia, Egypt; and†Hepatology Research Group, Peninsula College of Medicineand Dentistry, University of Plymouth, Plymouth, UnitedKingdom.

Address requests for reprints to Dr Mohammed El-AwadyGrawish, Oral Biology Department, Faculty of Dentistry, Man-soura University, Miet El Amel, Aga, Mansoura, Dakahlia35516, Egypt. E-mail address: Grawish2005@yahoo.com0099-2399/$ - see front matter

Copyright ª 2011 American Association of Endodontists.doi:10.1016/j.joen.2011.06.033

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The thin slices were then mounted on a glass slide, stained withhematoxylin-eosin, covered, and viewed under light microscope.

DiscussionTreatment planning involves appropriately selecting cases, deter-

mining how difficult the treatment might be to perform on a specific

individual, and sequencing treatment procedures to achieve a healthy and functional dentition (15). Vital pulp therapy performed timely and with effective biocompatible pulp-capping materials as an alterna-tive to routine endodontic treatment contributes to the successful heal-ing andprotection of pulp vitality (16). The statusof the pulpat the timeof capping is the predominant factor in determining the healing of exposed pulps (17). The purpose of this report was to describe thehistopathologic alterations of the dental pulp in a patient with uncon-trolled hepatitis C and to alert clinicians to determine the type of pulptherapy for those patients.

Infection with HCV mainly affects the liver, but it has extrahepaticmanifestations. HCV plays an important role in the development of MC,renal syndrome, lymphoproliferative disorder, and diabetes (18). The

pathologic investigation of this case reported thickening, stenosis, andocclusion of the vessel wall, ectopic calcification of the pulp tissue inclose association with pulpal blood vessels, interrupted and vacuolatedodontoblastic layer in the coronal pulpchamber,with inflammatory cell infiltrate throughout pulpal tissue (Figs. 1 and 2). These findings might be attributed to the cryoglobulins that precipitated inside the walls of pulpalbloodvessels.It is knownthat HCV-induced MC leads to systemic vasculititis; the cryoproteins have large molecular weight and increaseblood viscosity, which might directly precipitate and induce thrombosisin small vessels of some tissues including the dental pulp. Our findings

are in accordance with Galossi et al  (19), who reported that MC isa systemic vasculitis characterized by the deposition of circulating im-munocomplexes in small and medium-sized blood vessels, resultingin clinical manifestations.

The pathophysiologic basis for the HCV-related complications isthought to be immunologic. The deposition of cryoglobulin might act as inflammatory mediator and induce immune-mediated reaction. Ferriet al  (20) reported that cryoglobulinemic vasculitis is caused by  vascular deposition of circulating immune complexes, mainly cryoglo-bulins, and complement, with the possible contribution of both hemor-heological and local factors. Altered dental pulp tissue quality might be

attributed to cryoglobulins that had been precipitated within the micro- vasculature and led to tissue blood flow restriction and tissue hypoxia.This explanation is in compliance with Ramos-Casals et al  (21), whostated that cryoglobulinemia leads to systemic vasculitis because of inflammation of the vessel walls induced by the deposition of IgM-IgGcomplexes and subsequent complement activation or causes anischemic phenomenon because of a direct obstruction of vessels. Thepatient in this study did not have a history of regular HCV treatment,and the long-term chronic infection seems to be the main risk factorfor the histopathologic alterations.

TABLE 1. Representative Case Reports in Past Decade Describing the Effects of HCV-associated Cryoglobulinemia on Different Tissues and Organs

Blood vessels Erythema induratum ornodular vasculitis (6)

Polyarteritis nodosa (7)Renal Vasculitis complicated with

membranous proliferativeglomerulonephritis (8)

Polyarteritis nodosa andcryoglobulinemicglomerulonephritis (9)

Skin Cutaneous vasculitis (10)Palpable purpura (11)

Systemic Systemic lupuserythematosus (12)

Central nervous system Cerebral vasculitis (13)

Figure 1. Photomicrograph of coronal pulp tissue ( A) and radicular pulp tissue ( B ) showing thickening, stenosis, and occlusion of vessel wall (BV), ectopiccalcification of pulp tissue in close association with pulpal blood vessels (EC), interrupted and vacuolated odontoblastic layer (O), disorganized pulpal tissue

 with inflammatory cell infiltrate (DC) (hematoxylin-eosin stain; original magnification, 100Â).

Figure 2. Photomicrograph at area of dentin-pulp complex showing disorga-nization of pulp tissue with inflammatory cell infiltrate throughout the pulpal tissue (hematoxylin-eosin stain; original magnification, 200Â).

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 Acknowledgments

The authors deny any conflicts of interest related to this study.

References1. Plancoulaine S, Mohamed MK, Arafa N, et al. Dissection of familial correlations in

hepatitis C virus (HCV) seroprevalence suggests intrafamilial viral transmission andgenetic predisposition to infection. Gut 2008;57:1268–74.

2. Sharma SD. Hepatitis C virus: molecular biology and current therapeutic options.

Indian J Med Res 2010;131:17–34.3. BoyerO, Saadoun D,AbriolJ, et al.CD4+CD25+ regulatory T-celldeficiencyin patients

 with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 2004;103:3428–30.4. Cacoub P, Costedoat-Chalumeau N, Lidove O, Alric L. Cryoglobulinemia vasculitis.

Curr Opin Rheumatol 2002;14:29–35.5. Terrier B, Sene D, Dechartres A, et al. Systemic vasculitis in patients with hepatitis C

 virus infection with and without detectable mixed cryoglobulinemia. J Rheumatol 2011;38:104–10.

6. Fernandes SS, Carvalho J, Leite S, et al. Erythema induratum and chronic hepatitis Cinfection. J Clin Virol 2009;44:333–6.

7. Della Rossa A, Tavoni A, Lorefice P, Casula F, Bombardieri S. HBV and HCV infec-tion, polyarteritis nodosa and mixed cryoglobulinaemia: a case report. Clin Rheu-matol 2000;19:502–4.

8. Lo KY, Chen CY, Lee CS. Hepatitis C virus-associated type II mixed cryoglobulinemia  vasculitis complicated with membranous proliferative glomerulonephritis. Ren Fail 2009;31:149–52.

9. Canada R, Chaudry S, Gaber L, Waters B, Martinez A, Wall B. Polyarteritis nodosa and cryoglobulinemic glomerulonephritis related to chronic hepatitis C. Am JMed Sci 2006;331:329–33.

10. Groves C, Devereux C, McMillan C. A case of cutaneous vasculitis with underlyinghepatitis C and cryoglobulinaemia. Ulster Med J 2008;77:51–3.

11. Cecchi R, Giomi A, Paoli S. Palpable purpura at the site of previous herpes zoster inassociation with mixed cryoglobulinemia and hepatitis C virus infection. J Dermatol 2001;28:256–8.

12. Niewold TB, Swedler WI. Systemic lupus erythematosus arising during interferon-alpha therapy for cryoglobulinemic vasculitis associated with hepatitis C. Clin Rheu-matol 2005;24:178–81.

13. Arena MG, Ferlazzo E, Bonanno D, Quattrocchi P, Ferlazzo B. Cerebral vasculitis ina patient with HCV-related type II mixed cryoglobulinemia. J Investig Allergol Clin

Immunol 2003;13:135–6.14. Smith AJ. Vitality of the dentin-pulp complex in health and disease: growth factors askey mediators. J Dent Educ 2003;67:678–89.

15. Stewart T. Diagnosis and treatment planning are essential prior to commencingendodontic treatment: discuss this statement as it relates to clinical endodonticmanagement. Aust Endod J 2005;31:29–34.

16. Glickman GN, Seale NS. AAE and AAPD symposium overview: emerging science inpulp therapy—new insights into dilemmas and controversies. J Endod 2008;34(Suppl):S1.

17. Ward J. Vital pulp therapy in cariously exposed permanent teeth and its limitations. Aust Endod J 2002;28:29–37.

18. Zein NN, Abdulkarim AS, Wiesner RH, Egan KS, Persing DH. Prevalence of diabetesmellitus in patients with end-stage liver cirrhosis due to hepatitis C, alcohol, orcholestatic disease. J Hepatol 2000;32:209–17.

19. Galossi A, Guarisco R, Bellis L, Puoti C. Extrahepatic manifestations of chronic HCV infection. J Gastrointest Liver Dis 2007;16:65–73.

20. Ferri C, Zignego AL, Pileri SA. Cryoglobulins (review). J Clin Pathol 2002;55:4–13.21. Ramos-Casals M, Trejo O, Garcıa-Carrasco M, Cervera R, Font J. Mixed cryoglobu-

linemia: new concepts. Lupus 2000;9:83–91.

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