1068 Ann Rheum Dis 2001;60:1068–1069 Ann Rheum Dis: first published as 10.1136/ard.60.11.1068 on 1 November 2001. Downloaded from Polyarteritis nodosa and mixed cryoglobulinaemia related to and C virus coinfection

P Garcia de La Peña Lefebvre, L Mouthon, P Cohen, F Lhote, L Guillevin

Abstract On admission, the physical examination was Objective—To determine the responsibil- unremarkable. Blood analyses showed white ity of hepatitis B virus (HBV) and hepati- blood cell count 14×109/l, with 10×109/l, tis C virus (HCV) and therapeutic neutrophils; erythrocyte sedimentation rate implications in a patient who developed 100 mm/1st h; alkaline aminotransferase 149 systemic . U/l (normal <37); aspartate aminotransferase Case report—The case of a 38 year old 249 U/l (normal <50); glutamyltransferase 300 woman who had a past history of addic- IU/l (normal <50); normal bilirubin <17 tion to intravenous drugs and developed µmol/l; proteins 59 g/l (normal 62–78); albu- after infection by HBV min 19 g/l (normal 38–48); á1 globulin 4.12 g/l and HCV is described. The clinical and (normal 1–2.5); á2 globulins 11.9 g/l (normal laboratory findings substantiated not only 4–6.5); â globulins 4.5 g/l (normal 5.5–8.5); ã the diagnosis of polyarteritis nodosa globulins 16.8 g/l (normal 7–16); IgG 17.5 g/l (PAN) but also that of mixed cryoglobulin- (normal 6.8–12.7); IgA 2.07 g/l (normal 0.84– aemia with a monoclonal IgMê compo- 2.69); IgM 1.9 g/l (normal 0.7–1.99). nent. Renal function and parameters were normal. Conclusion—Because cryoglobulins are Antinuclear antibodies and antineutrophil cyto- rarely found in HBV related PAN but often plasmic antibodies were negative. Complement associated with HCV infection, and in fraction C4 was low, 0.08 g/l (normal 12–28); light of the histological findings, cryo- C3 was normal, 1.12 g/l (normal 0.75–1.4); globulinaemia was interpreted as being CH50 was normal, 95%; properdin 415 mg/l secondary to HCV infection. This example (normal 200–600 mg/l). Type II cryoglobuli- of a highly complex situation emphasises naemia with a monoclonal IgMê component the need to gather all relevant clinical, was detected and found to be 127 mg/l. biological, histological, and complemen- Anti-HCVantibodieswerefoundbyanimmuno- tary data so that the best treatment for enzymatic method and confirmed by a RIBA overlapping of distinct vasculitides can be III test. An HCV-RNA search was positive. selected. Hepatitis B surface antigen (HBsAg) and (Ann Rheum Dis 2001;60:1068–1069) hepatitis B e antigen (HBeAg) were present without evidence of the corresponding anti- http://ard.bmj.com/ The relation between viruses and vasculitis is bodies. HBV DNA was detected by hybrido- now well established: hepatitis B virus (HBV) is test. HIV-1 and HIV-2 serologies were nega- considered to be responsible for a minority of tive, hepatitis A virus (HAV) antigens and cases of polyarteritis nodosa (PAN),12 and antibodies were absent. Abdominal ultrasonog- virus (HCV) for more than 80% of raphy detected homogeneous hepatomegaly mixed cryoglobulinaemias (MC).3 Because of without evidence of splenomegaly or abdomi-

similar risk factors and routes of infection, sev- nal lymph nodes. on September 30, 2021 by guest. Protected copyright. eral viruses can be acquired simultaneously A deltoid muscle biopsy showed vasculitis of and cause diVerent diseases, and the optimal small and medium sized arteries and venules therapeutic strategy must be carefully consid- with leucocytoclasis and lymphocyte infiltrates, ered. but no fibrinoid necrosis. No immunofluores- Herein we describe a patient who developed cent study was performed. A hepatic biopsy Department of systemic vasculitis after HBV and HCV showed chronic hepatitis (Knodell scale = 11). Internal Médicine, Hôpital Avicenne, coinfection and discuss the responsibility of Ten days after admission to hospital she Université Paris-Nord, each virus and the therapeutic implications. developed paraesthesias of both hands; several 125, route de days later, , , and par- Stalingrad, 93009 Case report aesthesias in the left foot appeared. Electro- Bobigny CEDEX, In January 1995 a 38 year old woman myography detected axonal neuropathy. An France abdominal angiogram showed multiple micro- P Garcia de La Peña developed and , and lost Lefebvre weight. She had a past history of alcoholic of mensenteric, renal, splenic, and L Mouthon dependence that required specific treatment. hepatic arteries, with multiple stenoses and P Cohen She had also had a depression one year earlier. visceral infarcts. HBV related PAN was diag- F Lhote She had no prior history of hepatitis but had nosed, even though MC could also be consid- L Guillevin been addicted to intravenous drugs since 1984. ered owing to the muscle biopsy findings. Correspondence to: She had no permanent employment and her In April 1995, treatment was started accord- 4 Dr Mouthon two children were healthy. Six months before ing to the protocol described elsewhere. She luc.mouthon@ the first symptoms of vasculitis, she had a short received a daily methylprednisolone pulse for avc.ap-hop-paris.fr term sexual relationship with a man known to three days, followed by oral (50 Accepted 9 May 2001 be infected with replicating HBV. mg/day), which was rapidly tapered within 14

www.annrheumdis.com Polyarteritis nodosa related to hepatitis B and C virus coinfection 1069 Ann Rheum Dis: first published as 10.1136/ard.60.11.1068 on 1 November 2001. Downloaded from days. Thirteen plasma exchanges were per- of HBV related PAN.4 However, although formed within one month. After stopping ster- complete remission and absence of relapse is oids, treatment with interferon alpha-2b (3 rarely seen in MC, HCV related MC may also MU, three times a week) was prescribed for respond fairly well to interferon. The absence two months. of HCV replication three years after recovery Her condition improved after the second from vasculitis also supports recovery from plasma exchange; one month later the abdomi- MC. PAN may also be secondary to HCV nal pain disappeared and motor nerve palsy infection, as there are several reports of vascu- progressively regressed while paraesthesias litis aVecting abdominal organs in HCV persisted. Six weeks later, anti-HBe antibodies associated cryoglobulinaemic vasculitis.9 were detected, and cryoglobulinaemia became The clinical and laboratory findings substan- undetectable. tiated the diagnosis of PAN but also that of MC Three years later, the patient has only minor with a monoclonal IgMê component. Because left foot paraesthesias. Liver function is nor- cryoglobulins are rarely found in HBV related mal. Anti-HBs and anti-HBe antibodies, cryo- PAN but frequently associated with HCV globulins, and HCV serology remain positive, infection, and in light of the histological but HCV-RNA replication is undetectable. findings in our patient, we interpreted cryo- globulinaemia as being secondary to HCV Discussion infection. Indeed interpretation of the histo- The association of two virus related vascu- logical findings, is the crucial point. According litides in one patient is rare. The first studies on to the American College of MC showed a high incidence of HBV mark- classification,10 PAN can be diagnosed, but the ers,56 but this concept has changed since the Chapel Hill nomenclature11 would exclude this discovery of serological markers for HCV diagnosis. This example of a highly complex infection.3 situation emphasises the need to gather all rel- Galli reported that 3% of 350 patients with evant clinical, biological, histological, and MC had chronic HBV infections,7 whereas complementary data so as to select the best others found 17% HBV related cryoglobulin- treatment for overlapping of distinct vascu- aemia.8 litides. Although it is diYcult to establish defini- tively the diagnosis between HBV related PAN 1 Guillevin L, Lhote F, Cohen P, Sauvaget F, Jarrousse B, Lortholary O, et al. Polyarteritis nodosa related to hepatitis or HCV related MC, the response to treatment B virus. A prospective study with long-term observation of may help to interpret clinical data further. 41 patients. Medicine (Baltimore) 1995;74:238–53. 2 Guillevin L, Lhote F, Gherardi R. The spectrum of Despite the fact that some symptoms or bio- virus-associated vasculitides. Curr Opin Rheumatol 1997; logical and histological findings overlap, we 9:31–6. 3 Agnello V, Chung RT, Kaplan LM. A role for hepatitis C considered a diagnosis of PAN in our patient to virus infection in type II . N Engl J Med correspond best to all the data collected. The 1992;327:1490–5. 4 Guillevin L, Lhote F, Sauvaget F, Deblois P, Rossi F, Leval- rapid onset of clinical manifestations, biologi- lois D, et al. Treatment of polyarteritis nodosa related to cal evidence for a recent HBV infection, and hepatitis B virus with interferon-alpha and plasma exchanges. Ann Rheum Dis 1994;53:334–7. the short time between the probable sexual 5 Gocke DJ, Hsu K, Morgan C. Association between polyar- http://ard.bmj.com/ contamination and the occurrence of vasculitis teritis nodosa and Australia antigen. Lancet 1970;i:1149– 50. suggested that HBV was responsible. Diagnos- 6 Gocke DJ, McIntosh RM. Cryoprecipitates containing tic diYculties came, on the one hand, from the hepatitis B antigen in patients with liver disease. Gastroen- terology 1973;65:542. presence of multiple microaneurysms and 7 Galli M. Cryoglobulinemia and serological markers of arterial stenoses on the angiogram, which sug- hepatitis viruses. Lancet 1991;338:758–9. 8 Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin gests classical PAN, and on the other, from the M. Cryoglobulinemia in chronic liver disease: role of hepa- biopsy results which included vasculitis of titis C virus and liver damage. Gastroenterology 1994;106:

1291–300. on September 30, 2021 by guest. Protected copyright. small sized arteries, which tends to suggest 9 Cacoub P, Maisonobe T, Thibault V, Gatel A, Servan J, MC. In this patient with demonstrated coinfec- Musset L, et al. Systemic vasculitis in patients with hepati- tis C. J Rheumatol 2001;28:109–18. tion, clinical and virological evolution sup- 10 Lightfoot RW Jr, Michel BA, Bloch DA, Hunder GG, Zvai- ported the hypothesis that clinical manifesta- fler NJ, McShane DJ, et al. The American College of Rheu- matology 1990 criteria for the classification of polyarteritis tions might have been secondary to PAN and nodosa. Arthritis Rheum 1990;33:1088–93. not MC. The recovery from all symptoms and 11 Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides. Proposal the absence of relapse once HBV replication of an international consensus conference. Arthritis Rheum had stopped is also suggestive of the diagnosis 1994;37:187–92.

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