On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.1 Rio de Janeiro Jan./Feb. 2004
Erythema nodosum and infection by hepatitis C virus*
Thelma SkareI; Rafael BonanII
Professor of Rheumatology, Faculdade Evangelica de Medicina do PR (FEPAR)
IISixth year medical student - FEPAR
Hepatitis C virus is an RNA virus that causes chronic hepatitis in 75% of infected individuals.1 As much the acute infection as the chronic may be asymptomatic or may course with only slight and unspecific symptoms. Because of this the disease is often detected quite late, when the medicines used for its treatment have a reduced effectiveness.2
An early diagnosis of this disease can be facilitated if the doctor is alert in recognizing the symptoms that are not hepatic, such as those that are dermatological in nature. The following have been reported as being associated with the infection by hepatitis C virus: vasculitis due to cryoglobulinemia,2 late cutaneous porphyria,1,2 lichen planus,1,2 vitiligo,2 polyarteritis nodosa1 and generalized pruritus.1
In this paper a case is presented involving infection by hepatitis C virus in a 28-year-old pregnant woman and the diagnosis was confirmed by the presence of erythema nodosum.
This patient had a history of red and painful nodules in the lower limbs. They had begun appearing intermittently two years previously. She had used a glucocorticoid for a short while, in an unsuccessful attempt to resolve the problem. At the time of the consultation the patient was not using any medication, except for the sporadic use of some paracetamol tablets. She denied having any articular symptomatology, photosensitivity or vasomotor phenomena. She had a history of mild alopecia and oral ulcers. A former-smoker, she was seven months pregnant, this being her third pregnancy. She had not had similar symptoms in the previous pregnancies. Physical exam showed normal vital signs; precordial auscultation showed normal rhythmic sounds, indicating clean lungs. The abdomen had a uterine increase compatible with 28 weeks of pregnancy and without other visceromegaly. Bilaterally in the skin of the pre-tibial area she presented lesions compatible with those of erythema nodosum (Figure 1).
Biopsy of a cutaneous lesion revealed the presence of nodular areas with an inflammatory infiltration of histiocytes, lymphocytes and a few neutrophiles. This was associated with areas of necrosis in the reticular dermis and in the fatty tissue. The BAAR test was negative.
The laboratory investigation showed: LE cells, rheumatoid factor, negative VDRL and PPD tests negatives, ANF positive in low titer (1/80). Assays for autoantibodies, such as anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, and cryoglobulins were negative. The dosage of Antistreptolysin-O was normal. Chest X-ray test was postponed in view of the pregnancy. Testing for hepatic function showed SGOT (serum glutamic-oxaloacetic transaminase) at 118U/L (normal is up to 30U/L) and SGPT (serum glutamic-pyruvic transaminase) at 102U/L (normal is up to 20U/L). Serology for HCV was positive, and this infection was confirmed by PCR (polymerase chain reaction). Placement by genotyping was subtype 3a.
Because of the positivity for hepatitis C, delivery by cesarean section was programmed. Soon after the child's birth, the patient was referred to another service for hepatic biopsy and where she was treated with ribavirin and interferon. By telephone contact eight months after the biopsy and treatment, the patient affirmed that she was feeling well, with no further recurrence of the cutaneous lesions to date.
Erythema nodosum is a form of hypersensitivity expression mediated by cells that are manifested clinically by the onset of subcutaneous nodules. These are painful and located most commonly in the extensor surfaces of the legs. They may be accompanied by fever, arthralgia or arthritides and lymphadenopathy.3
Several diseases can trigger their appearance, including infections, sarcoidosis, Crohn's disease, lymphomas and even the use of certain medications. The greater or lesser prevalence of one or another cause of this disease depends on the population being studied, since the causes tend to vary from region to region.4
Pregnancy has been implicated in cases of erythema nodosum,3 and, in the described case, there existed the possibility that the pregnancy itself was involved in the etiological process. However, this patient had been suffering recurrent outbreaks for two years, beginning at a time when she was not pregnant.
Infection by hepatitis C virus as a cause of erythema nodosum has already been reported,3,5,6 even so, this association is not frequently recognized. Although in the case presented here the fact that hepatitis cannot be implicated directly in the etiopathology of the process, the presence of erythema nodosum enabled a diagnosis of hepatic disease and early institution of treatment. Furthermore, this diagnosis indicated the need for cesarean section to reduce the risks of vertical contamination of the child during delivery.
1. Bonkovsky LH, Mehta S. Hepatitis C: a review and update. J Am Acad Dermatol 2001;44:159-79.
2. Schwabwer MJ, Zlotogorski A. Dermatologic manifestations of hepatitis C infection. Int J Dermatol 1997;36:251-4.
3. Dixey JJ. Erythema nodosum In Klippel J, DieppePA. Rheumatology 2nd Ed, Ed Mosby, London,1998; Sec 5; 25. 1-4
4. García-Porrua C, González-Gay MA, Vásquez-Caruncho M et al. Erythema nodosum, Artrithis Rheum 2000;43(3):584-92.
5. Domingo P, Rios J, Martinez E, Casas F. Erythema nodosum and hepatitis C (letter). Lancet 1990; 336:1377.
6. Terver MNG, Modiano P, Gogolewski S, Gaucher P, Schmutzb JL. Erythème nouex rélélateur dúne hépatite C chronique active (letter). Presse Medicale 1995;24 (26):1221.
Thelma L Skare
João Alencar Guimarães, 796
80310-420 Curitiba PR
Tel./fax: (41) 274-1659 / 240-5082
in April, 29th of 2002
Approved by the Consultive Council and accepted for publication in June, 13th of 2003
* Work done at Reumatology Service of "Hospital Universitário Evangélico de Curitiba- Paraná".