CUTANEOUS MANIFESTATIONS OF HEPATITIS B and C VIRUS

INFECTIONS

Marie-Sylvie DOUTRE

Bordeaux

(France)

Various dermatologic disorders are associated with viral hepatitis infections, sometimes revealing these infections.

Several cutaneous manifestations are associated with hepatitis C virus infection

The relation between HCV infection and some cutaneous manifestations is now clearly demonstrated

So, there are several arguments for the part of HVC in mixed cryoglobulinemia

HCV RNA sequencesare concentrated in the cryoprecipitate and detected in cutaneous lesions

Agnello Arthritis Rheum 1997

Dermatologic findings include infiltrated purpura,livedo reticularis, legs ulcers, sometimes associated with arthritis, neuropathy, nephropathy…

The efficacy of alpha interferon in about 50% of patient is also an argument for the role of HCV in mixed cryoglobulinemia

Sometimes, there are conflicting responses to treatment for liver and

cryoglobulinemia

The association HCV-cryoglobulinemia is frequent : anti-HCV antibodies are detected in about 85% of cryoglobulinemia

However, a clear relationship between HCV infection and cryoglobulinemia has not been etablished with

- HCV genotypes- viral load- genetic factors

There are rare case-reports of cutaneous vasculitis without cryoglobulinemia

HCV infection has also reported in case reports or small series of polyarteritis nodosa

Cacoub J Rheumatol 2001

It’s the same for porphyria cutanea tarda

High prevalence of HCV markers (50 to 90%) have been reported in sporadic PCT from Italy, Spain and France.Lower rates, but significant higher than in the corresponding general population, have been reported in other countries

Recently, an increased frequency of hemochromatosis gene mutations (C282Y, H63D) has been detected in patients with sporadic PCT, suggesting a synergistic action of genetic factors with extrinsec factors

Egger Dig Dis Sci 2002

For other dermatosis, some studies indicate a relationship, some others do not. So, the link between oral Lichen Planus

and HCV infection is always contreversial

Lodi Br J Dermatol 2004

It’s the same for pruritus

There are aspecific lesions such as xerosis, excoriations, prurigo

Several factors contribute to the pruritus

- cholestasis- direct effect of HVC- treatments (interferon, ribavirin)

Fisher J Am Acad Dermatol 1994Cribier Acta Dermatol Venereol 1998

A lymphocytic sialadenitis does occur in patients with HCV infection

This is often associated with xerostomia but it is not associated with xerophtalmia or with anti SSA antibodies

Ramos- Casals Medicine 2005

Anecdotal dermatologic disorders have been reported in HCV infected patients

Urticaria

Erythema nodosum

Erythema multiform

Necrolytic acral erythemaAbdallah J Am Acad Dermatol 2005

Dermatological manifestions are also observed during acute and/or chronic phase of HBV infection

PARSONS Int J Dermatol 1996PYRSOPOULOUS Curr Gastroenterol Rep 2001

URTICARIA during the pre-icteric phase of HBV infection, association with fatigue, headache, arthralgia

DIENSTAG Ann Med Int 1978

There is a lymphocytic or leucocytoclastic vasculitis

HBs antigen deposits are observed in the small vesselsNEUMANN

Br J Dermatol 1981

Chronic urticaria is rarely associated with HBV infection

DOUTRE Presse Med 1987

CUTANEOUS VASCULITIS

cutaneous vasculitis can be associated with arthralgia, renal or neurological manifestations

vasculitis can occur during acute or chronic phase of HBV infection

SERGENT Medicine 1976

The role of HBV in mixed cryoglobulinemia is contreversial HBV markers are observed in high

proportions of patients with type II or III cryoglobulins LEVO N Engl J Med 1977

HBs antigen is present in the cryoprecipitate

However, HBV DNA is rarely demonstrated in these patientsCACOUB Arthritis Rheum 1992

POLYARTERITIS NODOSA

In the seventies, the prevalence was estimated to be 30 to 40 %, at present, about 7 %

Mouthon Pathol Biol 1999 Trepo Autoimmun 2001

the cutaneous manifestations are similar

some manifestations are more common in HBV related PAN : abdominal signs, renal failure, arterial hypertension, orchitis

mortality is not different in two types of PAN

Guillevin J Int Med 1989

treatment is different with short course of steroid therapy, plasma exchanges and anti viral drugs

Guillevin J Rheumatol 1989

GIANOTTI-CROSTI syndromeThe role of HBV infection was discovered in the seventies

GIANOTTI Br J Dermatol 1970

The eruption is associated with an anicteric hepatitis

CAPUTO J Am Acad Dermatol 1992

in fact, many different virus can be associated with this eruption (EBV, HBC, CMV, adenovirus, HHV-6...)

CHUH Pediatr Dermatol 2002TERASAKI Dermatology 2003

LICHEN PLANUS

The link between L.P. and chronic hepatitis has been etablished.REBORA Int J Dermatol 1984

The frequency of HBV markers is between 4 to 40 % but the replication of HBV was not demonstrated

At present, the link between L.P. and HBV infection is difficult to etablish

>> all studies were published when serological detection of HVC was not available

PORPHYRIA CUTANEA TARDAHBV markers are frequently associated with PCT but HBs antigen was

present in only few casesROCCHI Liver 1986 VALLS J Dermatol 1986

the series were published before the serological tests for HCV are available

OTHER TYPES OF CUTANEOUS ERUPTION ARE OBSERVED

photolocalized eruption

KAYAKAWA Br J Dermatol 1996

papular purpuric gloves and socks

GUIBAL Lancet 1996

Some cutaneous manifestations can appear during the treatment

of viral infection

Cutaneous reactions represent 5 to 17 % of side effects observed in patients receiving Interferon, «classic» alpha INF or peg-interferon, alone or in combination with ribavirin

DALEKOS Eur J Gastroenterol Hepatol 1998

Hair loss, itching, xerosis and eczematous lesions are the most frequent adverse cutaneous manifestations

Sookoian Arch Dermatol 1999Manjon-Haces Acta Derm Venereol2001Kerl Br J Dermatol 2003

Most patients showed clinical improvement with symptomatic treatment.

However, some patients abandoned nterferon because of these side-effects

Dereure Br J Dermatol 2002

Induction or exacerbation of psoriasis, lupus, lichen, vitiligo, autoimmune bullous dermatosis has been also described

Georgetson Am J Gastroenterol 1993Doutre Gastroenterol

Clin Biol 1996

Cutaneous and systemic sarcoidosis have been reportedRamos-Casals Medicine 2005

Others cutaneous side-effects are also reported here and there Straightening of hair Bessis Br J Dermatol 2002

Lanigan Br J Dermatol 2003

Meyerson’s phenomenomKrischer J Am Acad Dermatol 1999

Girard Br J Dermatol 2005

Skin and cutaneous hyperpigmentation Willems Br J Dermatol 2003

Local reactions are also observed such as erythema, induration

Much less frequently, necrosis is observed, no dependent on the site of injection or the dose

The exact mechanismsremain unknown

The extension of HB vaccination has led to the appearance of dermatologic side effects

The tolerance of HB vaccine is generally good.However, some dermatologic manifestations have been observed in children and adults.

MAC MAHON Am J Med 1992 AUBIN Rev Fr Allergol 1994

urticaria and angiooedema BARBAUD Br J Dermatol 1998

lichen planus Numerous observations in the literature since the first case

reported in 1990 by CIACCIO and REBORA

systemic and cutaneous leucocytoclastic vasculitis Some thirty cases in the literature

polyarteritis nodosa DE FAYSER Clin Exp Rheumatol 2000 BOURGEAIS Ann Dermatol Venereol 2003

systemic lupus erythematosus TUDELA Nephron 1992 MAMOUX Arch Pediatr 1994 GUISERIX Nephron 1996 FINIELZ Nephrol Dial Transplant 1998

Other manifestations are observed more rarely

Generalized granuloma annulare WOLF Eur J Dermatol 1998

Erythema multiform WAKEEL Br J Dermatol 1992 LOCHE Clin Exp Dermatol 2000

Erythema nodosum DI GIUSTO Lancet 1986 GOOLSBY N Engl J Med 1989

cutaneous lupus erythematosus and buccal aphtosis GREZARD Ann Dermatol Venereol 1996

pityriasis rosea like-eruption DE KEYSER Clin Exp Rheumatol 2000

Gianotti-Crosti syndrome HANG Hautartz 2002

For these adverse reactions, it is still debated whether there is a causal association or a simple coincidence.

"Sequence is not consequence"

CALES Gastroenterol Clin Biol 2001

Reactions are also described at the injection site. They are usually transient, erythema, itching, oedema.

COSNES Contact dermatitis 1990

KAABER Contact dermatitis 1992

SKOWRON Contact dermatitis 1997

Sometimes, painful erythematosus nodules apparead, due to aluminium

Other local reactions are observed

localized lichenoid reaction due to thiomersal STAURIANEAS Dermatology 2002

lipoatrophy VILETTE Ann Dermatol Venereol 1997

necrobiotic granuloma AJITHKUMAR Clin Exp Dermatol 1998

Considering the very low proportion of affected patients in comparaison with all subjects immunized (in France, 27 millions in 1998), an individual predisposition seems very likely.

Vaccination with HBV is effective and safe

Thank

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