Selective IgA Deficiency and Aseptic Liver Abscess as Initial Indicators of Crohn’s Disease in a Young Woman: A Case Study

Introduction

Diagnosing a hepatic lesion in a young woman with no previous medical history can be challenging, resulting in multiple diagnostic hypotheses, such as infectious liver abscess (bacterial or parasitic), benign tumor including hemangioma or liver adenoma, and malignant tumor (hepatocellular carcinoma or metastatic liver cancer). To achieve an accurate diagnosis, we need to consider the patient’s medical history (eg, travel, past diseases), clinical features (eg, fever, pain, digestive disorders), biological test findings (abnormal liver function tests, biological inflammatory parameters, tumor markers, and microbiological exams including cultures, polymerase chain reaction [PCR] and serologies), and tomodensitometry or magnetic resonance imaging (MRI).

Crohn’s disease (CD) is reportedly associated with liver damage, especially diffuse granulomas [1] and aseptic abscess, which have been reported in liver studies [2]. The histologic analysis of CD typically exhibits granuloma.

Immunoglobulin A (IgA) is the most prevalent immunoglobulin in the body; it is mainly involved in mucosal immunity and is found as a dimer in the gastrointestinal tract [3]. IgA deficiency is the most frequent primary immunodeficiency and can be challenging because it is usually asymptomatic; only 30% of cases are symptomatic with development of infection, autoimmunity, or cancer [3,4]. According to the European Society of Immunodeficiencies, selective IgA deficiency (SIgAD) refers to an undetectable or less than 7 mg/dL concentration of serum IgA in patients above 4 years old with normal immunoglobulin G and M levels, normal vaccine response, and no secondary causes of hypogammaglobulinemia and T-cell defects. Recently, IgA deficiency has been associated with celiac disease or inflammatory bowel disease (IBD) including CD [4].

In this report, we present the case of a young woman with fever and a 4-cm hepatic lesion associated with concomitant nonspecific digestive symptoms that led to the discovery of CD associated with SIgAD.

Case Report

On May 2023, a 23-year-old woman with no prior medical history other than appendicitis complicated by peritonitis in 2021 presented to the Emergency Department with acute dyspnea. Her fever (38–40°C) had persisted for more than 2 weeks; transient diarrhea also occurred but resolved within a few days. Furthermore, she reported arthromyalgias and 2 episodes of vomiting with no associated abdominal pain. While abdominal echography results were normal, tomodensitometry performed in the Emergency Department revealed hypodense lesions on the right liver lobe, indicating a hepatic abscess. Upon admission, biological results were as follows: C-reactive protein, 96 mg/L; leukocytes, 11.6 G/L; PNN, 9.36 G/L; Hb, 11.9 G/dL; aspartate transaminase, 81 UI/L; alanine aminotransferase, 134 UI/L; PAL, 150 UI/L; gamma-glutamyl transferase, 82 UI/L; LDH 263 UI/L; and ferritin, 215 µg/L. Viral serologies for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, VHA, VHB, VHC, and VHE were negative or related to a past infection. In addition, bacterial and parasitic serologies (toxoplasmosis, echinococcosis [alveolar and hydatidosis], amoebiasis, distomatosis, schistosomiasis, trichinellosis, bilharziasis Q fever, and bartonellosis), as well as blood, stool, and urine cultures, were all negative. Although autoantibodies and lymphocyte immunophenotyping were within the normal range, immunoglobulin assessment revealed an isolated IgA deficiency (IgA <0.05 g/L, with normal IgG and IgM). Negative results were obtained for digestive tumor markers (ACE, CA19-9, and AFE) and the QuantiFERON test, and the conversion enzyme assay result was within normal levels. The lung X-ray result was normal. Hepatic MRI showed a 4-cm lesion of the hepatic dome (Figure 1), associated with other smaller lesions of the dome and segments IV and VII. Additionally, positron emission tomography-computed tomography revealed hypermetabolism in the lesion and the surrounding lymph nodes and hyperfixation in the digestive tract and on the pelvis.

No antibiotics were administered, and 2 ultrasound-guided liver biopsies showed no conclusive lesion during anatomopathological or microbiological analysis (bacteriological and microbiological cultures or PCR analyses, including 16S RNA). A third sample was assessed with laparoscopy and biopsy of the lymph nodes. Anatomopathological findings revealed a gigantocellular epithelioid granuloma with caseous-free necrosis and some granulomas with numerous eosinophilic polynuclei (Figure 2). This third biopsy also obtained negative microbiological culture and PCR results. Colonoscopy with gastroscopy was also performed to assess for IBD. Signs of celiac disease and familial granulomatosis were searched for. Eventually, we found moderate terminal ileal involvement compatible with CD. Ileal and gastric biopsies (carried out systematically) revealed necrotizing gigantocellular epithelioid granulomas associated with mucosal inflammation and patchy ulceration (Figure 2). The samples also had negative microbiological examination results. However, fecal calprotectin levels increased to 485 µg/g. The patient was then diagnosed with CD and started on infliximab and azathioprine treatment, leading to regression of digestive and general symptoms. Nine months after hospitalization, MRI showed regression of the liver abscess (Figure 1) and absence of biological inflammatory syndrome.

Discussion

This clinical case report describes the discovery of aseptic liver abscess with concomitant discovery of a SIgAD as an initial atypical manifestation of CD in a young woman. Generally, liver abscesses indicate pyogenic or parasitic liver abscesses, especially in patients without a previous medical history of CD. Our patient had negative results in a thorough microbiological assessment, without undergoing antibiotherapy, but she had SIgAD. Histological analysis revealed an aseptic and granulomatous lesion without caseous necrosis. Endoscopic investigation confirmed CD occurrence. CD is a cause of granulomatous hepatitis mimicking liver abscess, which is sometimes the first manifestation of CD, such as in our case [5]. However, these aseptic abscesses are rare CD manifestations and correspond to gigantocellular granuloma, which is the result of autoinflammatory manifestations. These autoinflammatory processes are also responsible for other extraintestinal manifestations, often described in IBD as inaugural symptoms (but not present in our patient), such as pyoderma gangrenosum, erythema induratum, oral ulceration, and anal abscess [6]. The comb sign (hypervascular appearance of the mesentery) in active CD [7] was not detected on the radiologic exams performed. The literature concerning liver aseptic abscess is limited to case reports and case series. However, in these reports most patients received antibiotics before liver biopsy, indicating that pyogenic liver abscess was suspected. These case series and reports did not use formal radiological diagnostic criteria for differentiating between aseptic abscess (AA) versus pyogenic abscess. Therefore, AA was retained as a diagnosis in a patient with radiological evidence of deep abscesses but without infection. Radiological findings cannot easily differentiate pyogenic liver abscess from granulomatous liver abscess [8,9]. Therefore, pyogenic liver abscesses should always be ruled out, as they frequently occur among patients with CD [10].

IgA functions in gut homeostasis are essential; thus, IgA deficiency can lead to gut infection as well as IBD. IBDs, including celiac diseases and CD, are frequently reported in patients with IgA deficiency [4,11–13]. Gut dysbiosis and lack of integrity of the digestive barrier, as well as an exaggerated immune response to commensals, may explain the association between IBD and SIgAD [14,15]. Common variable immunodeficiencies (CVID) are also associated with granulomatous diseases mimicking CD, highlighting the close relationship between immunoglobulin deficiencies and granulomatosis [16].

Generally, granulomas develop in response to microbial or insoluble agents [17]. They can increase intestinal mucosal permeability because of the ulceration. Additionally, the loss of integrity of the normal mucosal barrier can play a significant role in granuloma formation, including in the liver. Thus, a low level of IgA, owing to its important functions in gut homeostasis, can cause increased loss of integrity and granuloma formation [18]. Therefore, selective IgA deficiency can be related to inflammatory bowel diseases as well as an atypical manifestation such as aseptic liver abscess. Interestingly, in CVID, IgG levels are low but are associated with at least 1 other Ig, including IgA; therefore, the role of IgA deficiency in CVID and granulomatous lesions cannot be ruled out.

Although associations between aseptic liver abscess and CD and between IgA deficiency and CD have been reported, this case report, to the best of our knowledge, is the first to present a case of CD manifesting both SIgAD and aseptic liver abscess. This case illustrates the importance of immunoglobin dosage, including IgA, in diagnosis of SIgAD in case of suspicion of CD, as a low level may suggest CD. Currently, data on CD severity during IgA deficiency are lacking, and cohort studies describing CD manifestations in patients with IgA deficiency including aseptic liver abscess are warranted.

Conclusions

CD should be considered in aseptic liver abscess cases. Due to the association between IgA deficiency and IBD, including CD, IgA, and IgG/IgM should be assessed in patients with suspected or proven IBD to rule out SIgAD or common variable immunodeficiency. However, further studies describing patients with IgA deficiency and CD are necessary to determine if specific manifestations such as aseptic liver abscess are more frequent in this association.