Perihepatitis as an Initial Manifestation of Systemic Lupus Erythematosus

Abstract

A 25-year-old man presented with a fever and right upper quadrant abdominal pain. Computed tomography (CT) of the abdomen revealed diffuse perihepatic capsular enhancement, suggesting perihepatitis. Although the patient was a man, Fitz-Hugh-Curtis syndrome was suspected based on the CT findings. Treatment with several antibiotics was ineffective. Urinary tract infection was ruled out due to negative urinary bacterial screening and careful history taking. He was finally diagnosed with systemic lupus erythematous (malar rash, pleuritis, positive antinuclear antibody, and positive anti-ds-DNA antibody). Perihepatitis resolved quickly with high-dose prednisolone. Perihepatitis may be the first manifestation of SLE.

Introduction

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by genetic and environmental factors. Women are predominantly affected compared to men, at a ratio of 8-15 to 1 (1). Clinical manifestations in SLE are highly variable, including rash, a fever, polyarthritis, nephritis, neuropsychiatric disorders, and cytopenia. Serositis is one of the clinical manifestations of SLE and occurs as pleuritis or pericarditis. The incidences of pleuritis and pericarditis among SLE patients are 15-34% and 10-24%, respectively (2). Peritonitis is a less common form of serositis in patients with SLE.

Fitz-Hugh-Curtis syndrome (FHCS) is a chronic condition of pelvic inflammatory disease due to Chlamydia trachomatis or Neisseria gonorrheae infection and is often described as perihepatitis: inflammation of the liver capsule without involvement of the liver parenchyma. FHCS starts with bacterial infection of the female reproductive system and then progresses to the pelvic cavity and perihepatic area. Given its predominance in women, case reports of FHCS in men are uncommon (3).

Perihepatitis has rarely been reported in patients with SLE (4-6), especially in men (6). We herein report a case of perihepatitis in a man with SLE as an initial manifestation.

Case Report

A 25-year-old man presented to a local doctor complaining of Raynaud's phenomenon. Laboratory findings revealed positive antinuclear antibody (ANA; 5,120×) with a speckled pattern and positive anti-U1-ribonucleoprotein (RNP) antibody (256×), but no other significant laboratory abnormalities were observed. Mixed connective tissue disease was suspected, but there were no other symptoms except for Raynaud's phenomenon. However, the findings disappeared when the weather began to grow warmer as the seasons changed.

Nine months later, he was admitted to another hospital due to a fever and right upper quadrant abdominal pain. Laboratory findings revealed a leucocyte count of 9,000 /μL (lymphocytes, 19.7%) and C-reactive protein (CRP) level of 4.31 mg/dL. Neither proteinuria nor hematuria was observed on a urinalysis. Contrast-enhanced computed tomography (CT) of the abdomen revealed diffuse perihepatic capsular enhancement in the early phase (Figure). Perihepatitis due to FHCS was suspected, and antimicrobial therapy with cefozopran and levofloxacin was administered for a week, with no effects. He was subsequently transferred to our hospital.

Figure.

Contrast-enhanced abdominal CT demonstrated an enhanced rim surrounding the right lobe of the liver (arrow), which is consistent with perihepatitis. CT: computed tomography

On history taking, he denied any sexual activity. A physical examination revealed positive Murphy's sign. Laboratory findings were as follows: leucocyte count, 6.4×10³/μL (lymphocytes, 1.0×10³/μL); hemoglobin level, 12.9 g/dL; platelet count, 185×10³/μL; CRP, 9.21 mg/dL; total bilirubin, 0.69 mg/dL; aspartate transaminase, 29 U/L; alanine transaminase, 22 U/L; immunoglobulin G (IgG), 1,244 mg/dL; complement component C3, 147 mg/dL (normal 73-138); C4, 28 mg/dL (normal 11-31); ANA, positive (2,560×) with speckled pattern; anti-ds-DNA antibody, 20.6 IU/mL (normal <12); anti-U1-RNP antibody, positive (256×); anti-SS-A antibody, negative; and anti-Sm antibody, negative. Repeated urinalyses revealed no abnormalities. Serum anti-C. trachomatis IgG and IgA were negative. Both urinary C. trachomatis and N. gonorrheae RNA were negative. One additional week of empiric antimicrobial therapy with ceftriaxone and minocycline showed no effect. During hospitalization, facial erythema developed, and abdominal pain spread from the right upper quadrant to the left upper quadrant. Repeated contrast-enhanced CT examinations performed three weeks apart showed residual enhancement around the liver and bilateral pleural effusions with right-sided predominance. A small amount of ascites was observed in the pelvic cavity. Given the absence of a history of sexual activity and negative urinary tract infection, FHCS was ruled out. The patient was then diagnosed with perihepatitis associated with SLE following the exclusion of other diagnoses and the satisfaction of the SLE classification criteria (malar rash, pleuritis, positive ANA, and positive anti-ds-DNA antibody) (7). The SLE disease activity index score was 7 (new rash, a fever, pleuritis, and positive anti-ds-DNA antibody). Abdominal pain and perihepatitis resolved quickly with oral prednisolone (65 mg, 1 mg/kg/day).

After the prednisolone dose was tapered to 9 mg/day, proteinuria developed 1 year after discharge. The urinary protein level was 1.5 g/gCr, and the complement component C3 level was 82 mg/dL, whereas anti-ds-DNA antibody was negative. A renal biopsy revealed lupus nephritis class V (lupus membranous nephropathy). Retreatment with combination therapy of high-dose prednisolone, mycophenolate mofetil, and tacrolimus was started. Urinary proteins gradually decreased, and belimumab was added nine months later to reduce the prednisolone dose.

Discussion

We reported a rare case of perihepatitis as the initial manifestation of SLE. The diagnosis of FHCS was ruled out by careful history taking and urinary and serological examinations. The treatment response to glucocorticoids was good, but lupus nephritis developed one year later, along with tapering of the prednisolone dose.

FHCS is considered unlikely in the present case. It occurs in women as a rare extrapelvic complication of genital bacterial infection. In previous case reports of FHCS in men, the diagnosis was based on typical radiographic imaging findings, positive urine specimens for C. trachomatis or N. gonorrheae DNA, and the effectiveness of antibiotics (3,8). In contrast, the RNA tests for both C. trachomatis and N. gonorrheae were negative in the present case, and multiple antibiotics were ineffective. Furthermore, the patient denied any sexual activity. Pleural effusion is usually absent in patients with FHCS. In addition, there are only a few case reports that have described a small amount of pleural effusion (9,10). Pericardial effusion associated with FHCS has never been reported.

Perihepatitis is rarely described as a manifestation of SLE (4-6). In four previous cases published in the English literature, all patients presented with abdominal pain in the right upper quadrant and showed enhancement in the rim of the right lobe of the liver on contrast-enhanced CT (Table) (4-6). However, our patient also presented with a fever. In addition, an elevation of both CRP and hepatic enzymes, if present, has tended to be mild in previously reported cases, but this was not true in our present case. Furthermore, apart from the present case, SLE was diagnosed prior to the diagnosis of perihepatitis.

Table.

Previous Case Reports of Perihepatitis in Systemic Lupus Erythematosus.

Case (ref. No.)	Age/ Sex	Time from SLE onset (years)	Chief complaint	Other complaints	CRP (mg/dL)	Hepatic enzymes	Other organ involvement	Treatments
1[4]	45/W	NA	Acute abdominal pain in the right upper quadrant	None (no fever, arthralgias and rash)	NA	Mild transaminitis	NA	Dosage increase of immunosuppressive agents
2 [5]	29/W	NA	One-week history of worsening constant right upper quadrant pain	None (no fever, vomiting, anorexia, change in bowel habit and pelvic pain)	2.2	γ-GTP, 71 U/L; ALP 154 U/L	Primary PH	Oral oxycodone and paracetamol
3 [6]	42/M	7	Two-week history of severe dry cough and right upper quadrant pain	NA	1.7	NA	LN (class IV)	Antibiotics (vibramycin, amikacin) and oral PSL
4 (our case)	25/M	0	Acute abdominal pain in the right upper quadrant	Fever	9.21	Normal	None (LN developed later)	PSL 65 mg

ALP: alkaline phosphatase, CT: computed tomography, CRP: C-reactive protein, γ-GTP: gamma glutamyl peptidase, LN: lupus nephritis, M: man, NA: not available, PH: pulmonary hypertension, PSL: prednisolone, SLE: systemic lupus erythematosus, W: woman

Whether or not perihepatitis due to SLE is part of the manifestation of abdominal serositis (peritonitis) remains unclear. Peritonitis is a less common form of serositis in patients with SLE (11). Although the pathological mechanism of peritonitis in SLE is unclear, a few cases of lupus peritonitis demonstrated immune complex deposits and inflammatory infiltrates in the peritoneal tissue (12,13). In contrast, the peritoneum in FHCS comprises fibrotic inflammatory tissue between the liver capsule and peritoneum. A definite diagnosis of FHCS can be made by laparoscopy, which reveals adhesions between the diaphragm and the liver or the liver and the anterior abdominal wall, often referred to as “violin string-like adhesions” (14). However, no patients with lupus perihepatitis underwent laparoscopy. Given the quick response to glucocorticoid treatment and the presence of bilateral small effusions in our patient, we suspect that perihepatitis might have been a limited form of serositis.

In conclusion, we encountered a man with perihepatitis as the initial manifestation of SLE. Although rare, SLE should be considered one of the differential diagnoses of perihepatitis when FHCS is ruled out by careful history taking and bacteriological examinations.

The authors state that they have no Conflict of Interest (COI).