Rash and arthralgia caused by hepatitis E

A 52-year-old woman came to her general practitioner with pain, swelling, and stiff ness in her shoulders, elbows, hips, knees, and ankles. She also had bilateral retro-orbital pain, eye discharge, and headache for a week, and loss of appetite for 4 days. 2 days before her appointment, she developed a maculopapular, non-itchy rash all over her body. She was a non-smoker and consumed moderate amounts of alcohol. The general practitioner requested baseline blood tests including full blood count, liver and renal function tests, rheumatoid factor, auto-antibodies and complements, prescribed analgesia, and referred the patient to a rheumatologist. When reviewed by the rheumatologist 2 weeks later, the patient’s left second and third metacarpophalangeal joints were tender. There was no evidence of conjunctivitis, rash, or synovitis. Radiological analyses of her hands and feet were unremarkable. Investigations requested by the general practitioner were reviewed by the rheumatologist: liver function tests were abnormal (alanine amino transferase 1025 U/L [10–50 U/L]; alkaline phosphatase 177 U/L [40–125 U/L]; gamma glutamyl transferase 224 U/L [5–35 U/L]). Bilirubin was normal (11 μmol/L) (3–21 μmol/L). Ferritin (1593 μg/L) (15–200 μg/L), C-reactive protein (25 mg/L) (0–5 mg/L) and erythrocyte sedimentation rate (39 mm/h) (3–15 mm/h) were raised. Her full blood count, renal function, and coagulation profi le were within normal limits. Complement C3 was raised (1·7 g/L) (0·81–1·57 g/L) but C4 was normal (0·23 g/L) (0·13–0·39 g/L). Rheumatoid factor, anti-nuclear/anti-smooth muscle antibodies were not detected, whereas anti-dsDNA (17·5 IU/mL) (0–15 IU/mL), extractable nuclear antigen, antimitochondrial antibody (187·1 IU/mL), and anti-Ro (SS-A) antibody (68·7 U/mL) were detected. Hepatitis B surface antigen and hepatitis B core total antibody were not detected. HIV and hepatitis C virus screening tests were requested by the rheumatologist. In view of abnormal liver function tests, further tests were added to exclude other causes of viral hepatitis. Hepatitis A IgM was undetectable. There was serological evidence of past cytomegalovirus and Epstein-Barr virus infections. Hepatitis E virus (HEV) IgM and IgG were detectable; however, HEV RNA was not detected in the sample sent by the rheumatologist. The blood sample sent previously by the general practitioner was retrospectively investigated and acute hepatitis E was diagnosed on the basis of detectable HEV RNA and evolving seroconversion. HEV RNA was sequenced (ORF2 region as described previously) and identifi ed as genotype 3. During the ensuing 6 weeks, the patient’s liver function returned to normal, and clinical signs and symptoms resolved. On subsequent interview by the local Health Protection Team, the patient did not report any travel outside Scotland during the incubation period (previous 9 weeks). Furthermore, no specifi c association with food or other risk factors could be established. Most (98%) HEV infections are asymptomatic. Symptomatic individuals typically have non-specifi c symptoms such as myalgia, arthralgia, weakness, and vomiting. Some develop jaundice with transaminitis. Acute hepatitis E presenting as polyarthritis with longlasting viraemia (up to 7 months) has been reported in an individual who travelled to Egypt during the incubation period. By contrast, viraemia was short lived in our case. Until recently, HEV infection in developed countries was thought to be travel-associated. However, autochthonous HEV, a zoonotic infection caused predominantly by HEV genotype 3, is now recognised in many developed countries. We have previously reported autochthonous hepatitis E genotype 3 from Scotland, with an individual infected with multiple strains of HEV genotype 3. Recently, HEV genotype 3 has been detected in a substantial proportion of mussels harvested along the west and east coasts of Scotland, suggesting a possible transmission route, although a direct epidemiological link is yet to be established. Since HEV screening is not routine in most UK clinical laboratories, acute hepatitis E is probably underreported. Our case highlights the variable presentation of acute hepatitis E and the importance of hepatitis E screening in individuals with transaminitis, irrespective of travel history.