Unusual Presentation of Systemic Lupus Erythematosus in a Young Male: A Case Report

Abstract

Hepatic involvement in systemic lupus erythematosus (SLE) is common but described infrequently. Liver is usually never the primary organ to be affected in lupus. Again hepatic involvement probably does not carry much prognostic importance though it may correlate with lupus activity. We here report a case of 21-year-old man with no prior comorbidity or addiction who presented to us with acute hepatic illness with jaundice. He also had malar rash and arthralgia. Viral markers were negative. Antinuclear antibody and anti–double-stranded DNA (dsDNA) were strongly positive. Liver biopsy was consistent with autoimmune hepatitis, whereas skin biopsy was suggestive of SLE. He had a brisk and complete recovery with prompt use of immunosuppressive agents (corticosteroids and azathioprine). Cyclophosphamide was started latter in view of lupus nephritis. This is probably the fourth reported case of SLE presenting as acute hepatic illness with jaundice.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various autoantibodies, systemic inflammation mediated by the complement system. The aetiopathogenesis of SLE is multifactorial and influenced by various genetic, environmental and hormonal factors.¹ The disease primarily affects young women of child bearing age and is diagnosed on basis of presence of 4 of 11 criteria as identified by American College of Rheumatology (ACR) that develop either sequentially or simultaneously. These features include malar rash, discoid rash, photosensitivity, oral ulcerations, nonerosive arthritis, pleuritis, pericarditis, renal disorders (proteinuria/hematuria) and neurological disorders (seizures and psychosis). Along with these, few haematologic and immunologic disorders are also included in the ACR criteria.² Treatment of this illness is primarily carried out by immunosuppressive agents including corticosteroids.²

Involvement of liver in SLE is common in the form of mildly elevated transaminases, which is seen in up to 60% of patients.³ Hepatic involvement may occur due to SLE itself (lupus hepatitis).⁴ However, associated conditions such as chronic hepatitis B and C, acute viral hepatitis A or E, autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) may also lead to hepatic impairment. Finally, various immunosuppressive drugs including corticosteroids, azathioprine that are commonly used in these patients may also affect the liver. Jaundice as the presenting symptom of lupus is confined to few case reports only. Here we describe a rare presentation of SLE as acute hepatic illness with jaundice.

Case report

A 21-year-old male patient presented with a 2-month history of generalized weakness, dull aching abdominal pain along with pain in large and small joints of upper limb. There was also history of morning stiffness, however, there was no joint swelling or redness over joints. Along with these symptoms, he developed maculopapular rashes over upper trunk, hands and feet. He also developed erythematous rashes over face, around nasal bridge and cheeks with sparing of nasolabial folds. The rashes were spontaneous in onset, painless, not associated with any associated symptoms including itching or discharge. After 15 days of onset of these symptoms, he developed progressive yellowish discolouration of eyes and skin which was associated with pruritus and yellow coloured urine. He was shown to a local practitioner and was prescribed some herbal medications. However, the symptoms continued to worsen, and he was admitted to Department of Gastroenterology, Kalinga Institute of Medical Sciences,Bhubaneswar.

On admission, he had deep jaundice with maculopapular lesions on his face, hands, chest and abdomen(Figure 1, Figure 2, Figure 3). On examination of abdomen, there was hepatosplenomegaly. The rest of systemic examination were normal.

Figure 1.

Maculopapular rashes over face.

Figure 2.

Maculopapular rashes over face.

Figure 3.

Maculopapular rashes over palms.

On evaluation, the haemoglobin level was 8.4 gm/dL, total leucocyte count (TLC) was 11 × 10⁹/L and platelet count was 350 × 10⁹/L. Mean corpuscular haemoglobin, mean cell haemoglobin concentration and red cell distribution width were above normal suggestive of anaemia of chronic disease. He had serum bilirubin of 38 mg/dL (cut-off value 1.3 mg/dL) with direct bilirubin of 33.1 mg/dL. His aspartate transaminase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) level were 4277 IU/L, 576 IU/L and 310 IU/L, respectively, suggestive of predominantly hepatocellular pattern of liver injury. There was reversal of albumin to globulin ratio. International normalizing ratio and prothrombin time were within the normal limits. All the viral markers including IgM serology for hepatitis A virus (HAV), hepatitis E virus (HEV) were negative. Hepatitis B surface antigen serology was negative. Serum complement levels were low. Antinuclear antibody (ANA) was weakly positive, whereas anti–double-stranded DNA (dsDNA) was strongly positive. Antismith antibody and antineutrophil cytoplasmic antibody were negative. Total serum immunoglobulin (IgG total) was 2340 mg/dL (cut-off value 1600 mg/dL). Urine routine/microscopy examinations were not suggestive of proteinuria or haematuria. Ultrasonography of abdomen revealed hepatosplenomegaly, mild ascites and bilateral pleural effusion. Portal vein, hepatic veins and inferior vena cava were normal. Magnetic resonance cholangiopancreatography (MRCP) showed normal intrahepatic and extrahepatic bile ducts. Gastroduodenoscopy was normal. Based on these investigations, the possibility of SLE with seronegative acute viral hepatitis with prolonged cholestasis was kept. Other diseases such as drug-induced liver injury (DILI), SLE-AIH overlap syndrome and SLE-PSC overlap syndrome were also considered.To confirm the diagnosis, he underwent percutaneous liver biopsy. Liver biopsy showed mild widening of the portal tracts with mixed inflammatory cell infiltration and occasional lymphoid aggregates. Hepatocytes showed occasional giant cell transformation and rossetting (compatible with AIH).⁵ There was also feathery degeneration of hepatocytes along with severe canalicular and hepatocytic cholestasis (Figure 4, Figure 5). These histological features were suggestive of a mixed cholestatic and hepatocellular pattern of liver injury. However, there were no ductopenia, lobular granulomas or periductal fibrosis characteristics of primary cholestatic disorders such as PBC/PSC.⁶ Taking into account, all these clinical features and investigations, his AIH score was 6 as per the simplified criteria suggested by International AIH Group classification thus suggestive of probable AIH.⁷

Figure 4.

Liver biopsy, H & E (400×), portal tract showing moderate degree of mixed inflammatory infiltrate (Lymphoplasmacytic and few polymorphs along with mild interface hepatitis).

Figure 5.

Liver biopsy, H & E (400x), Feathery degeneration and rosseting of hepatocytes.

Skin biopsies were taken from the affected areas which showed focal hyperkeratosis with parakeratosis of epidermis, basal cell degeneration and mild chronic inflammatory infiltrate of dermoepidermal junction. The pathological findings in skin biopsy were consistent with SLE (Figure 6, Figure 7). Based on these investigations, he was started on prednisolone (40 mg/day). Ursodeoxycholic acid was also started in view of cholestatic symptoms such as pruritus although its clinical benefits in this conditions is uncertain.⁸ Gradually serum bilirubin and ALT levels decreased, and he was discharged on prednisolone and azathioprine. At discharge, serum bilirubin, AST and ALT were 2 mg/dL, 78 IU/L and 120 IU/L, respectively.

Figure 6.

Skin biopsy, H & E (200×), hyperkeratosis, parakeratosis, thinning of epithelium, subepithelial cleft, dermal fibrinoid deposits.

Figure 7.

Skin biopsy, H & E (400×), Basal vacuolar degeneration, chronic inflammatory and mucinous deposits in dermis.

However, he stopped all the medications and did not come for follow-up for 2 months. Afterwards, he presented with high grade fever with eruptive skin lesions and extensive oral ulcerations. On evaluation, he had anaemia with haemoglobin of 8 gm/dL and leucocytosis (TLC-13.4 × 10⁹/L). Peripheral smear examination revealed microcytic hypochromic type anaemia. His serum urea and creatinine level were 56 mg/dL and 1.7 mg/dL, respectively. He also had elevated transaminases with AST and ALT of 750 IU/L and 330 IU/L, respectively, with normal bilirubin and ALP levels. Blood culture grew Staphylococcus aureus, which was sensitive to vancomycin and teicoplanin. Routine and microscopic examination of urine revealed significant proteinuria and haematuria. He was started on intravenous dexamethasone, piperacilin-tazobactam and vancomycin. Dexamethasone was administered as patient was unable to take oral prednisolone owing to oral ulcerations and bleeding from these ulcers. Gradually, his liver and renal functions improved, skin and mucosal lesions disappeared and he became afebrile. He was discharged on hydroxychloroquine and oral prednisolone. However, he continued to have proteinuria. Possibility of lupus nephritis was kept, and he was advised renal biopsy. However, patient denied the same in view of financial constraints. After explaining possible risk and benefits, he was started on cyclophosphamide for lupus nephritis. Currently, he is on regular follow-up in gastroenterology and rheumatology outpatient departments. His liver and renal functions are now within normal limits.

Discussion

Hepatic involvement in SLE can be divided into three categories. The most common being lupus hepatitis which is a liver dysfunction owing to lupus itself. The second category is other common diseases of liver that may occur in patients with SLE (viral hepatitis, vascular diseases of liver). The third category of illness includes overlap of lupus with other immunological conditions such as AIH, PBC, and PSC.⁹

Lupus hepatitis is an SLE-related subclinical liver dysfunction characterized by elevated transaminases.⁴ Incidence of lupus hepatitis is usually higher with active SLE than inactive disease state (11% vs 3%).Overall, incidence of lupus hepatitis in SLE is about 3–9%. Elevated antiribosomal P antibody titre is characteristically present in these patients. Liver biopsy in these patients usually shows lobular inflammation.¹⁰ These features may be particularly helpful to distinguish lupus hepatitis from other chronic liver diseases seen in these patients. Finally, elevated liver enzymes seen in these patients usually normalize after treatment with steroids.⁹

This case described a rare initial presentation of lupus in a young man. Previously only three cases have been reported with similar type of presentation (Table 1). As with other autoimmune diseases, lupus in male is rare comprising only 4%–22% of SLE in different series.¹¹ Male patients with lupus tend to have more renal, cardiovascular and neurologic involvement compared with females as described in various series.¹² Although our patient had characteristic dermatological manifestations and serositis, there was no cardiovascular or renal involvement. Although, involvement of liver has not been shown to have any sex predilection, hepatomegaly has been described more commonly in males as seen in our patient.¹² In most cases of SLE, renal, neurologic and cardiovascular involvement precede hepatic involvement. In contrast, our patient had acute hepatitis as the first presentation.

Table 1.

Published Case Reports of SLE Presenting as Acute Hepatitis.

Case	Age (years)	Sex	Clinical presentation	Investigations	Liver biopsy	Clinical course
Kawai T et al,92005	27	Female	Low grade fever, fatigue and dyspnoea for 1 week On examination – Icterus	Serum Bilirubin-9 mg/dL, AST- 473 U/L,ALT- 857 U/L,ANA/Anti-ds DNA-Positive,24-h urinary protein-2 gm/day, Viral Serology-Negative	Not done	Improvement with Prednisolone
Rodriguez VE et al,102008	27	Female	Jaundice, pain abdomen and malar rash	Transamnitis, proteinuria, ANA/ASMA/Anti–dsDNA-strongly positive, viral markers – negative	Suggestive of autoimmune hepatitis	Improvement with prednisolone
Barosa R et al,112013	48	Female	Known case of SLE on hydroxychloroquine, corticosteroids and naproxen presented with anorexia, nausea and jaundice after restarting medications	Serum bilirubin- 11.8 mg/Dl, AST – 1270 U/L, ALT – 1740 U/,Prolonged PT by 9 s, IgG total-2.72 mg/dL (cut-off value 1.6) ANA – strongly positive Rest autoimmune markers and viral markers – negative	Suggestive of autoimmune hepatitis	Improvement with prednisolone
Our case	21	Male	Generalized weakness,arthralgia, morning stiffness, malar rash, jaundice and pruritus	Serum bilirubin-38 mg/dL, AST-4277 U/L, ALT-576 U/L, ANA-weakly positive, Anti–ds DNA – Strongly positive, viral markers – negative	Features compatible with autoimmune hepatitis severe intrahepatic and canalicular cholestasis also present	Improvement with prednisolone and Azathioprine

ALT, Alanine aminotransferase; ANA, Antinuclear antibody; ASMA, Antismooth muscle antibody; AST, Aspartate aminotransferase; ds DNA, Double-stranded DNA; SLE, Systemic lupus erythematosus.

Another unusual point to be noted in our patient was extremely high serum bilirubin and transaminases. Serum ALP was also elevated. Differential diagnosis of acute hepatitis in patients with SLE includes acute viral hepatitis related to HAV, HEV, hepatitis B virus, DILI, rarely overlap syndromes such as AIH, or PSC.

In this patient, all the viral markers were negative. Similarly, although there was history of intake of herbal medications, they were taken for few days after onset of symptoms including jaundice. The likelihood that liver injury can be attributed to a particular medication is determined by Roussel Uclaf Causality Assessment Method score. The score consists of 8 separate factors in 7 categories. The total score ranges from −9 to 14. Score more than 8 indicates that the liver injury is most probably attributed to the drug. However, the score should never be calculated when insult occurs after onset of symptoms.^13,14 Here, we would like to emphasize further that even though intake of herbal medications was after onset of jaundice and other symptoms, the cholestatic picture present in liver biopsy is difficult to explain with SLE alone. It might be due to intake of these medications. MRCP carried out was also suggestive of normal intrahepatic and extrahepatic bile ducts excluding large duct PSC. ANA was weakly positive, whereas anti–ds DNA was strongly positive. Positive anti–ds DNA is highly specific for diagnosis of SLE although it can also be seen in about half of patients with AIH.¹⁵ There was also hypergammaglobinemia and reversal of albumin-to-globulin ratio which can be seen in both SLE and AIH. Concomitant AIH and SLE have been reported infrequently (2.1–3.7%) in various series.¹⁶ These patients may have clinical presentation such as acute hepatitis. Thus it is difficult to distinguish SLE associated hepatitis (lupus hepatitis) and AIH (lupoid hepatitis) based on clinical, biochemical and serological investigations only. Liver biopsy was carried out which was suggestive of features compatible with although not typical of AIH.⁵ Although there was canalicular and hepatocyte cholestasis in liver biopsy, there was no ductular changes excluding PSC or PBC. As per comparison with other reported cases, male sex and cholestatic hepatitis are the key differentiating features of present case. We believe, cholestasis could be related to use of herbal drugs, although, it is difficult to prove.

Our patient was diagnosed as SLE with probable AIH and was started on prednisolone and azathioprine following which he had a brisk response with normalization of serum bilirubin and transaminases. Unfortunately, patient was lost to follow-up, stopped all medications and got admitted with SLE flare. This episode was managed with intravenous dexamethasone and antibiotics following which he improved and was discharged.

SLE in males can present as acute hepatitis with extreme hyperbilirubinemia and elevated transaminases. AIH should be considered as an important differential diagnosis. Liver biopsy should be performed in all these patients to confirm diagnosis. Finally,prognosis is excellent in most of these patients with use of immunosuppressive agents.

CRediT authorship contribution statement

Dibya L. Praharaj: Conceptualization, Methodology, Writing - original draft. Bipadabhanjan Mallick: Visualization, Investigation. Preetam Nath: Writing - review & editing. Sarat C. Panigrahi: Writing - review & editing. Prasanta Padhan: Writing - review & editing. Nageswar Sahu: Writing - review & editing.

Conflicts of interest

The authors have none to declare.

Funding

None.