Lupus Enteritis With Concomitant Genitourinary Involvement as the Initial Presentation of Juvenile-Onset Systemic Lupus Erythematosus

Introduction

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with multiorgan involvement. The exact pathogenesis of SLE remains poorly understood, despite significant advances in recent decades. SLE has several phenotypes, with varying clinical presentations from mild mucocutaneous symptoms to severe multiorgan involvement [1].

Childhood-onset or juvenile-onset SLE (jSLE) affects approximately 15–20% of SLE patients under the age of 18 [2]. Patients with jSLE usually have more severe disease than those with adult-onset SLE. jSLE is rare, exhibiting an incidence of 0.3–0.9 per 100 000 child-years and a prevalence of 3.3–8.8 per 100 000 children [3]. Disease susceptibility is thought to be influenced by hormonal factors, as reflected by the pronounced female predominance in SLE (8–15: 1 overall), with relatively greater male representation in prepubertal age groups [4]. Unfortunately, there is no current standardized care strategy for juvenile SLE, and most treatment approaches are extrapolated from adult SLE management [5].

The prevalence of gastrointestinal manifestations in SLE ranges from 15–75% [6]. Intestinal wall inflammation in SLE patients is an ill-defined and infrequent cause of abdominal pain known as lupus enteritis, with reported incidences ranging from 0.2% to 9.7% [7]. According to Tu et al, pediatric SLE patients who present with abdominal pain are significantly more likely to have lupus enteritis than adults, and experience higher recurrence rates [8]. The clinical features of lupus enteritis include abdominal pain, vomiting, diarrhea, and fever, and it can lead to serious complications, including intestinal infarction, obstruction, and perforation [7]. Lupus peritonitis is another rare gastrointestinal complication, with no well-defined incidence rates [9].

The co-occurrence of urinary tract involvement in patients with lupus enteritis is well described, likely reflecting a shared vasculopathic and immune-complex–mediated mechanism [9,10]. Although uncommon, lupus cystitis has been reported to cause urinary symptoms despite unremarkable urinalysis. Ultrasound and computed tomography (CT) often reveal reduced bladder capacity and diffuse or irregular bladder wall thickening [11]. In 2 cohorts by Yuan et al and Koo et al, the rates of coexisting lupus enteritis and cystitis were 23% and 35%, respectively [9,10].

This report describes a previously healthy 16-year-old male adolescent with jSLE who presented with a 2-month history of high-grade fever, weight loss, and lymphadenopathy. Later, he developed multisystem disease, including lupus nephritis, enteritis, peritonitis, cystitis, and epididymo-orchitis. He was treated with induction therapy using corticosteroids and cyclophosphamide, followed by maintenance therapy with hydroxychloroquine and mycophenolate mofetil.

Case Report

A previously healthy 16-year-old male patient presented with a 2-month history of daily recorded fever of 39°C, lacking a diurnal pattern, accompanied by severe fatigue, anorexia, and significant unintentional weight loss of approximately15 kg. He reported intermittent, non-deforming arthralgia affecting the wrists, proximal interphalangeal joints, and both knees, without swelling, erythema, or morning stiffness. He also noted the development of mild, intermittent night sweats later in the course associated with painful cervical lymphadenopathy. He denied respiratory, gastrointestinal, neurological, urinary, or cardiovascular symptoms at presentation, and there was no history of recent travel, sick contacts, or exposure to tuberculosis. His past medical history was unremarkable. He was not taking any regular medications and denied the use of herbal or over-the-counter drugs. His family history was notable for a sister with type 1 diabetes mellitus and celiac disease, with no other autoimmune or rheumatological disorders.

As he was admitted for further evaluation as a case of pyrexia of unknown origin, the following differential diagnoses were considered: chronic infections (such as tuberculosis), malignancy, particularly lymphoma, or an underlying autoimmune or autoinflammatory disorder. Whole-body CT revealed several abnormal findings: mild generalized lymphadenopathy, hepatosplenomegaly, and mild ascites. Fever and systemic symptoms persisted despite a thorough investigation, which included negative blood cultures, a normal echocardiogram, a normal ferritin level, and a lymph node core needle biopsy showing only reactive lymphadenitis.

In the third week of hospitalization, the patient developed clinical and radiologic evidence of serositis and renal involvement, evidenced by bilateral pleural effusions on chest CT, significant new-onset proteinuria (2.2 g/24 h), and active urinary sediment. Immunological testing strongly supported the diagnosis of SLE, revealing a positive antinuclear antibody (ANA) titer of 1: 640 with a homogeneous pattern, in addition to the presence of anti-double-stranded DNA (anti-dsDNA) antibodies and anti-Smith antibodies. He fulfilled the 2019 European League of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) SLE classification criteria, scoring 21 points (11 in the clinical domain and 10 in the immunological domain), exceeding the minimum score of 10 required for classification [12].

During the same admission, he developed scrotal pain and swelling. Examination showed bilateral tender, edematous testes without erythema or fluctuance. Ultrasound confirmed bilateral epididymo-orchitis. Empirical antibiotics were initiated due to the concern of possible secondary infection. Given the bilateral involvement and the fact that he had already been receiving antibiotics, urology determined that the findings were unlikely to be the result of an infectious cause. Accordingly, the overall picture was considered more compatible with immune-mediated inflammation related to his underlying disease than with a primary infection.

He was started on pulse-dose intravenous methylprednisolone at 15 mg/kg/day for 3 days, followed by oral prednisolone at 1 mg/kg/day, along with hydroxychloroquine at 5 mg/kg/day. A renal biopsy was scheduled to further classify the renal involvement and guide subsequent immunosuppressive therapy.

Two days later, he developed severe acute abdominal pain, vomiting, and loose stools. A CT scan of the abdomen demonstrated mildly dilated small-bowel loops with mucosal hyperenhancement, in keeping with lupus enteritis (Figure 1), significant abdominopelvic free fluid (ascites), and diffuse bladder wall thickening consistent with cystitis. There was no radiologic evidence of mechanical obstruction or frank bowel ischemia at that stage. This rapidly progressed to a suspected inflammatory small-bowel obstruction secondary to lupus enteritis, managed conservatively with nasogastric decompression, further high-dose intravenous steroids, and antibiotics. He gradually improved, became afebrile, and his symptoms resolved.

The diagnostic paracentesis showed exudative fluid with a low serum-ascites albumin gradient (SAAG) (1 g/dL), elevated protein (1.67 g/dL), and no evidence of infection or malignant cells on fluid cytology, all of which were consistent with lupus peritonitis and supported the diagnosis of exudative serositis secondary to SLE. Over several days, approximately 6 liters of ascitic fluid were drained.

Renal biopsy was attempted but had to be cancelled twice due to uncontrolled blood pressure. Given the presumed lupus nephritis and multiorgan involvement, intravenous cyclophosphamide was initiated empirically as induction therapy at 500 mg/m2 administered monthly according to the National Institutes of Health (NIH) regimen.

After 7 months, prednisolone was successfully discontinued and he was maintained on hydroxychloroquine and mycophenolate mofetil 1 g twice daily, along with supportive therapy.

Table 1 summarizes the patient’s laboratory investigations at presentation and at the last follow-up.

Discussion

This case highlights an unusual presentation of jSLE characterized by prolonged fever, lymphadenopathy, and early gastrointestinal and genitourinary involvement.

SLE is a multisystem, chronic autoimmune disease with a wide variety of clinical presentations. Its onset in adolescent males is very uncommon and can be diagnostically challenging. The patient presented herein is a 16-year-old male adolescent whose illness initially manifested with protracted fever, lymphadenopathy, and constitutional symptoms suggestive of infection or malignancy, which subsequently evolved into a severe multiorgan flare of SLE with renal, serosal, gastrointestinal and genitourinary involvement. This complex presentation underscores the protean nature of pediatric lupus and illustrates how early manifestations may mimic those of other conditions, delaying a definitive diagnosis.

The presentation of our patient initially fulfilled the classical criteria for pyrexia of unknown origen, a well-described scenario in the literature where systemic inflammation precedes serological confirmation of SLE [13]. The combination of persistent fever, lymphadenopathy, and constitutional symptoms, as well as reactive lymphadenitis on biopsy and the lack of microbial growth in cultures, further complicated the diagnostic process.

Lupus enteritis is an uncommon gastrointestinal complication, and is typically associated with small-vessel vasculitis, immune complex deposition, and subsequent bowel wall edema [7]. In our case, CT findings of small-bowel wall thickening, mucosal hyperenhancement, and massive ascites were consistent with prior reports by Koo et al [10] and Kim et al [14], describing similar imaging patterns of bowel edema and engorged mesenteric vessels (“comb sign”). Early corticosteroid administration is necessary to reduce the risk of complications such as perforation or ischemia. The efficacy of early corticosteroid treatment was supported by our patient’s rapid improvement of gastrointestinal symptoms after receiving pulse methylprednisolone.

Of note, our patient also showed evidence of concurrent lupus cystitis, which is an uncommon but recognized companion of lupus enteritis. In accordance with Yuan et al [9] and Kim et al [14], who described the rare coexistence of lupus enteritis and lupus cystitis, our patient had diffuse bladder wall thickening and sterile urinary findings. This serves to support the consideration of lupus cystitis when urinary symptoms develop without evidence of infection, especially when they occur concurrently with lupus enteritis. This association indicates a common pathogenic mechanism involving immune complex deposition and small-vessel vasculitis [7,9,10]. Several studies have shown a link between lupus enteritis and lupus cystitis; however, concurrent epididymo-orchitis is seldom described. Urinary tract involvement occurred in approximately 23% and 35% of cases in 2 cohorts, respectively, yet no male reproductive manifestations were identified in these studies [9,10]. In our patient, lupus enteritis was accompanied by bladder involvement; however, the simultaneous occurrence of epididymo-orchitis in an adolescent male remains rarely described.

Secondary autoimmune epididymo-orchitis is a rare lupus manifestation. Clinical features include scrotal pain, swelling, tenderness, and fever, which may be unilateral or bilateral. Immune-mediated epididymo-orchitis represents one of the most distinctive aspects of our case and is seldom observed in lupus [15]. Boulis and Majithia described genitourinary involvement in a male patient with lupus/scleroderma overlap [16]. The presence of bilateral, symmetrical ultrasound abnormalities and failure to respond to antibiotics strongly suggests an immune-mediated etiology, which is consistent with previous cases of lupus orchitis. Immune-mediated mechanisms should be strongly considered in the context of atypical or bilateral testicular inflammation, particularly in patients with established SLE, as early recognition is critical, and autoimmune orchitis usually responds to immunosuppressive therapy rather than antibiotics [15,16].

Lupus nephritis remains one of the most serious manifestations of lupus; it affects 32% to 82% of jSLE patients. Lupus nephritis tends to develop earlier in jSLE patients, and progresses more aggressively than in adult-onset disease [17]. Our patient had early nephritis, which was consistent with these known pediatric patterns.

In addition to lupus nephritis, our patient developed lupus enteritis during the same disease flare, reflecting multisystem involvement necessitating systemic immunosuppressive treatment. Optimal treatment protocols for lupus enteritis rely on expert consensus and case studies due to a lack of randomized trials. ReCONNET, SLICC, and SLEuro have collaborated on a manuscript outlining treatment regimens for rare lupus manifestations. Most experts recommend intravenous cyclophosphamide (for severe cases) or mycophenolate mofetil (for less severe cases), with supportive care such as bowel rest, hydration, and electrolyte management [18]. The concept of early aggressive immunosuppression is supported by the overall improvement in symptoms, serological markers of disease activity, and proteinuria following cyclophosphamide induction.

To our knowledge, the coexistence of lupus enteritis, cystitis, and epididymo-orchitis in a male adolescent with jSLE has rarely been reported in the literature. In comparison with published cases, our patient’s illness was remarkable for a distinct constellation of lupus enteritis, cystitis, epididymo-orchitis, and nephritis occurring during the same disease flare. This pattern most likely reflects widespread small-vessel vasculitic activity and serosal inflammation, and may represent a particularly severe systemic flare phenotype in male patients with early-onset lupus.

A limitation of this report is the inability to perform a renal biopsy due to uncontrolled hypertension.

Key clinical takeaways from this case:

Conclusions

This case report describes a rare and severe multiorgan presentation of jSLE, including lupus nephritis, enteritis, peritonitis, cystitis and epididymo-orchitis in an adolescent male, initially presenting as pyrexia of unknown origin with lymphadenopathy that mimicked infection or malignancy. He had a favorable outcome with a dramatic response to pulse methylprednisolone and cyclophosphamide induction, indicating that severe multiorgan SLE can be reversible with early recognition and aggressive immunosuppression. Our case enriches the expanding literature by enhancing diagnostic awareness in rare lupus manifestations and supporting the role of a collaborative multidisciplinary approach in managing such complex presentations.