Clinical Infection and Immunity, ISSN 2371-4972 print, 2371-4980 online, Open Access |
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Case Report
Volume 2, Number 2-3, September 2017, pages 36-39
Diagnostic Dilemma: Lupus-Related Hepatitis Versus Autoimmune Hepatitis in Systemic Lupus Erythematosus
Bhupen Barmana, e, Arvind Nongpiurb, Vandana Raphaelc, Sameer Joshia, Taso Beyonga, Kaustubh Borad
aDepartment of General Medicine, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, Meghalaya 793018, India
bDepartment of Psychiatry, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, Meghalaya 793018, India
cDepartment of Pathology, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, Meghalaya 793018, India
dDepartment of Biochemistry, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, Meghalaya 793018, India
eCorresponding Author: Bhupen Barman, Department of General Medicine, North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS), Shillong, Meghalaya 793018, India
Manuscript submitted June 30, 2017, accepted July 11, 2017
Short title: Diagnosis of Hepatitis in SLE
doi: https://doi.org/10.14740/cii34w
Abstract | ▴Top |
Hepatic involvement in systemic lupus erythematosus (SLE) may occur due to several factors like hepatotoxic drugs, steatohepatitis, coincident viral hepatitis and autoimmune hepatic diseases. However, the differentiation between lupus-related hepatitis and autoimmune hepatitis remains a challenge to the clinician because of many similar features. We describe a case of a 24-year-old female with active SLE who presented with acute liver dysfunction without inflammatory changes or associated with drugs exposure. Lupus hepatitis of this patient was successfully treated with stabilization of liver function as well as other manifestations of SLE.
Keywords: Systemic lupus erythematosus; Autoimmune hepatitis; Autoantibodies
Introduction | ▴Top |
Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding auto-antibodies and immune complexes. About 25-50% cases develop abnormal liver tests in their lifetime [1, 2]. Hepatitis in SLE mostly occurs as an adverse effect of prior treatment with potentially hepatotoxic drugs or due to co-existing infection by hepatotropic viruses. After exclusion of these etiologies, the physician may be confronted with the dilemma of whether to classify the patient as a primary liver disease with associated autoimmune hepatitis (AIH) which was formerly described as lupoid hepatitis or lupus hepatitis as a manifestation of SLE [3]. We present a case of hepatitis occurring in an SLE patient in which no viral or drug-related etiology could be found. We review both entities and provide a simplified guide to help differentiate SLE-related hepatitis from AIH.
Case Report | ▴Top |
A 24-year-old woman presented with a history of fluctuating but persistent jaundice of 4 months duration. Three years back, she had manifested malar rash, episodic migrating polyarthritis associated with photosensitivity, excessive fatigue and diffuse alopecia and was diagnosed with SLE. Treatment with hydroxychloroquine, analgesics and steroid was started and she had a complete remission of disease after 6 months of therapy and she was continuing with only hydroxychloroquine. Four months before presentation, she started developing yellowish discoloration of skin and eyes followed by generalized weakness, loss of appetite, epigastric pain, and recurrent episodes of vomiting and low grade fever. There was no history of melena or hematemesis or any menstrual irregularities. Her sleep, bowel and bladder functions were normal. She had never received blood transfusion or contact with ill person in recent past. She had no history of long-term medications (other than given for SLE), herbal supplements or consumption of wild mushrooms. She is non-alcoholic, non-smoker and no history of drug abuse. On examination, she was conscious and oriented. The temperature was 38.9 °C, blood pressure was 106/58 mm Hg, pulse rate was 104 beats per minute, respiratory rate was 20 breaths per minute and oxygen saturation was 98%, while the patient was breathing ambient air. There was conjunctival icterus and skin was yellow with no spider angioma and palmar erythema. There was mild pallor, but no clubbing or lymphadenopathy. Her abdomen was soft with mild epigastric tenderness without any guarding and rigidity but had mild tender hepatomegaly. On neurological examination, speech and attention span was normal and there was no asterixis. On musculoskeletal examination, there was localized swelling and tenderness of joints, especially the distal interphalangeal joints of both hands, wrist and knee joints. Examinations of other systems were normal.
Her initial laboratory workup showed anemia with altered liver enzymes (Table 1). Her complete blood counts showed a moderate to severe, microcytic hypochromic anemia, normal leucocyte count and high erythrocyte sedimentation rate (ESR). Liver functions showed elevated aminotransferase levels with normal bilirubin and alkaline phosphatase. Her renal function test, serum electrolytes and coagulation profile were within normal range. Urine analysis revealed orange, cloudy urine, with a pH of 6.0, a specific gravity of 1.020, 3+ bilirubin, 1+ protein, and trace amounts of glucose and leukocytes. Urinalysis also revealed positive nitrites, 2+ squamous cells, and 3 - 5 white cells and 2 - 4 red cells per high-power field, with occasional bacteria. Serological markers for hepatitis B, hepatitis C and human immune deficiency virus (HIV) were non-reactive. An ultrasonography of abdomen showed mild hepatomegaly with ascitis. Chest X-ray and echocardiography were normal. Further investigations showed testing for antinuclear antibodies (ANA) was positive at 1:640 in a speckled pattern, and the titer of antibodies to double-stranded DNA was 1:2,560, which were diagnostic of SLE. Autoimmune markers of hepatitis (antimitochondrial antibodies, anti-Smooth muscle antibodies, and antibodies to liver-kidney microsomes) along with rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), anti-SCL 70 were negative. Liver biopsy was done which showed presence of macrovascular steatosis with mild periportal involvement with few lymphocytic infiltrates (Fig. 1). She was started with intravenous dextrose saline, tablet prednisolone 40 mg once daily, ursodeoxycholic acid and hydroxychloroquine (200 mg twice daily). There was gradual improvement of the symptoms with disappearance of clinical signs. There was also marked improvement of her hematological and biochemical parameters. The patient was discharged on maintenance dose of steroids and continues to do well in follow-up.
Click for large image | Figure 1. Mild chronic hepatitis with predominantly lobular inflammation with few lymphocytes and macrovascular steatosis. |
Click to view | Table 1. Laboratory Data in the Patient With Lupus-Related Hepatitis |
Discussion | ▴Top |
SLE is an autoimmune disease affecting multiple organ systems, kidneys being most commonly involved. Hepatic involvement in patients with SLE is well documented, but considered to be rare. The hepatic involvement caused by hepatotoxic drugs, coincident viral hepatitis, non-alcoholic fatty liver disease or concurrent AIH must be ruled out before diagnosing lupus-related hepatitis. Clinical and biochemical data may not clearly differentiate whether hepatitis is due to autoimmune involvement or purely lupus-related.
For diagnosing AIH in SLE, the patient must fulfill the American College of Rheumatology (ACR) criteria for SLE and International Autoimmune Hepatitis Group (IAIHG) criteria for AIH for which our case had a pre-treatment score of 8 and post-treatment score of 10 which rules out AIH (Table 2) [4]. Histological evidence is considered to be conclusive in differentiating SLE-related hepatitis and AIH. Histological demonstration of hepatitis compatible with AIH is the essential diagnostic criterion of AIH [5]. Histological examination of liver biopsy in hepatitis associated with SLE is predominantly lobular and occasionally periportal with a paucity of cellular infiltrates (Fig. 1). When inflammatory cells are present, they are predominantly lymphocytes. Fatty infiltration and multifocal hepatic death without inflammatory cell invasion have also been reported in SLE and found to be associated with markers for apoptosis. However, AIH shows periportal (interface) hepatitis with piecemeal necrosis associated with lobular activity, rosetting of liver cells or dense lymphoid infiltrates.
Click to view | Table 2. Evaluation of Autoimmune Hepatitis in Our Patient as Per IAIHG Scoring System |
Auto-antibodies may help in differentiating these two entities. ANAs can be found in both these conditions; however, anti-Smooth muscle and antimitochondrial antibodies are rare in SLE-related hepatitis (< 30%) and often found in low titers. Auto-antibodies to ribosomal P proteins were originally described in patients with SLE and have been associated with neuropsychiatric and renal disease. A significantly increased frequency of anti-ribosomal P antibody has recently been found in patients with SLE-associated hepatitis. This antibody appears to be strongly associated with lupus-related hepatitis and with a more severe form of hepatitis. Anti-ribosomal P antibodies were not detected in the patients with AIH [6-8].
Conclusion
Diagnostic dilemma to distinguish SLE-associated hepatitis from AIH associated with SLE constitutes a therapeutic predicament since the course of disease in the two conditions is different. Available biochemical parameters are often inconclusive; however, liver biopsy can help differentiate between the two entities. Presence of anti-ribosomal P antibody may be a useful marker of SLE-associated hepatitis to differentiate it from AIH and other liver dysfunctions in SLE patients without renal dysfunction or CNS lupus.
Support
None.
Conflicts of Interest
None.
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