Widespread rash as initial presentation of acute hepatitis E in a woman with well-controlled HIV

Introduction

Zoonotic hepatitis E (HEV) is becoming increasingly common in the United Kingdom. This case, notable for the marked skin rash, highlights the need to consider testing for HEV in patients with deranged liver function tests and a variety of extrahepatic symptoms.

Case report

A 45-year-old woman presented with a 2-week history of widespread purpuric and discoid rash. Past medical history included well-controlled HIV (HIV-1 RNA undetectable for over 3 years and updated CD4 count 419 cells/μL (31%); cirrhosis secondary to previous hepatitis C and alcohol; past, cleared hepatitis B; Kaposi sarcoma and previous injecting drug use (>10 years ago). Her antiretroviral therapy, abacavir, lamivudine and dolutegravir, was unchanged over 18 months, with no other current or recent medication. Lesions were itchy but not painful. She was systemically well without fever, arthralgia or myalgia. Examination revealed a widespread purpuric rash on the trunk, with larger discoid lesions on the lower legs (Figure 1), sparing the palms, soles and face. There were no new clinical manifestations of decompensated cirrhosis, with a few spider naevi consistent with previous examinations. Alanine transaminase (ALT) was 580 u/L (37u/L 2 weeks previously at the onset of the rash and baseline <30; upper limit of normal (ULN) 35), bilirubin 6 µmol/L (ULN 20 µmol/L) and alkaline phosphatase (ALP, ULN 130 u/L) 148 u/L. She described regularly eating pork products including those sold at a discounted price at a local pub.OPEN IN VIEWER

Abdominal ultrasound showed stable features of known liver cirrhosis from previous hepatitis C and alcohol, with liver texture as before, normal appearance of the bile ducts and no new pathology. Herpes simplex, varicella, adenovirus, parechovirus and enterovirus were not detected by polymerase chain reaction (PCR) of skin swabs, but bacterial swab cultured Staphylococcus aureus. Blood treponemal and autoimmune antibodies were negative and eosinophil count normal. A dermatology opinion was sought but no specific diagnosis made. A biopsy was not considered to be indicated and empirical and topical corticosteroids were recommended. Recurrence of Kaposi sarcoma was felt to be unlikely as the rash was not clinically consistent with this; CD4 count was 419 cells/μL and HHV-8 DNA was not detected.

Ten days after presentation, HEV IgG and IgM were reported as positive, indicating acute infection with HEV. Blood HEV RNA was 350,000 iu/mL and identified as genotype 3. Cryoglobulins were negative. One month after initial presentation, the rash had improved and the patient remained clinically well. ALT had normalised and HEV RNA was 210 iu/mL (Figure 2). IgM measurements at diagnosis, 3 weeks and 9 months, were +17.1, +11.0 and +1.9, respectively. IgG measurements on the same dates were +3.3, +16.6 and +19.3, respectively. Epstein–Barr virus and cytomegalovirus IgM were both negative as was Hepatitis B surface antigen. Hepatitis C RNA was undetectable throughout. Nine months after initial diagnosis, HEV RNA was no longer detectable, excluding chronic infection.OPEN IN VIEWER

Discussion

This case demonstrates rash as the presenting feature of acute HEV, with thorough investigation making other causes unlikely. The rash appeared, peaked and improved at the same time as HEV viraemia and transaminitis; HIV was well-controlled throughout, and drug reactions were unlikely with no new medications and a normal eosinophil count.

HEV is a single-stranded RNA virus of the Hepeviridae family. Acute infection is defined as persisting less than six months. ¹ Genotypes 1 and 2 are associated with endemic faeco-oral transmission in Africa, Asia and the Middle East. Genotypes 3 and 4 are associated with zoonotic infection via ingestion of infected meat products. ² Frequent sexual transmission has not been identified. ³

Genotypes 1 and 2 produce a more aggressive clinical illness, and 16% of those infected will develop a symptomatic acute hepatitis compared to 2% in those with genotypes 3 and 4. ⁴ The incubation period is two to 10 weeks, and the classical presentation is with mild fevers, anorexia, nausea and vomiting, tender hepatomegaly, jaundice and dark urine/pale stools. Fulminant hepatic failure can occur, causing an estimated 70,000 deaths worldwide annually. ⁵ In pregnant woman in the third trimester, mortality can be as high as 25%, compared to less than 1% in nonpregnant individuals. ⁵ People with HIV and low CD4 counts (<200 cells/μL) may have persistent or chronic infection, even with minimally raised ALT ⁶ although systematic review has not shown increased risk of HEV compared with HIV-negative people.^7,8

Positive IgM antibodies for hepatitis E should prompt reverse transcriptase PCR (RT-PCR) to confirm viraemia and genotype. ¹ Treatment is usually supportive, although ribavirin has been used in severe illness or in the immunosuppressed ⁹ who may experience chronic infection. ¹⁰

The commonest reported extrahepatic manifestations reported are neurological, occurring in 7.5% of individuals with acute hepatitis E. ¹¹ Rash has been reported in around 3% in some European series^12,13 and cryoglobulinaemia has also been reported. ¹⁴ We note one similar case report in the Lancet in 2013, describing a woman presenting with a widespread, maculopapular rash and transaminitis. She was found to have acute hepatitis E and symptoms resolved spontaneously. ¹⁵

Rashes in people with HIV are common, and zoonotic hepatitis E may be emerging as a more frequent cause, not listed in textbooks, which we should consider as a differential diagnosis in a variety of patient presentations.