Delayed Recognition of Systemic Lupus Erythematosus Presenting With Visceral Muscle Dysmotility and Chronic Mucus-Bloody Enteropathy: A Case Report

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems through immune complex–mediated inflammation [1]. If not promptly recognized and treated, it may result in life-threatening complications. The disease has a higher prevalence among Asian and African populations than among Western populations; the estimated prevalence is 30 to 50 per 100 000 individuals in Asia, compared with a global prevalence of approximately 61 per 100 000 [2,3].

According to the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria [4,5], organ systems most commonly involved in SLE include the musculoskeletal, cutaneous, renal, hematologic, and central nervous systems [6]. Although these manifestations are well documented, gastrointestinal involvement remains poorly characterized and is often underdiagnosed [7–10]. Gastrointestinal symptoms are identified in 15% to 75% of patients with SLE; they range from abdominal pain, nausea, and vomiting to pancreatitis and lupus enteritis, the most common cause of acute abdominal pain in SLE [5,11]. Lupus enteritis is rarely reported; its prevalence is 2.5% to 9.7% in Asian countries.

Intestinal pseudo-obstruction and visceral muscle dysmotility syndrome (VMDS) are rare gastrointestinal complications associated with SLE; they may coexist with ureterohydronephrosis. Early recognition is essential to prevent misdiagnosis and delayed treatment. To date, no previous reports have described chronic hematochezia as the initial manifestation preceding a diagnosis of SLE [12–20].

Here, we describe a 20-year-old woman who presented with chronic mucus-bloody diarrhea as the first manifestation of SLE, later complicated by lupus nephritis and neuropsychiatric lupus. This case emphasizes the importance of recognizing VMDS as an early and atypical gastrointestinal presentation of SLE. Given that gastrointestinal symptoms are often nonspecific and may mimic infectious etiologies, identification of lupus-related enteropathy requires a high index of clinical suspicion.

Case Report

INVESTIGATIONS:

Repeat laboratory testing showed pancytopenia with a positive direct Coombs’ test result. Peripheral blood smear demonstrated prominent microspherocytes. Liver function tests revealed elevated aspartate aminotransferase and gamma-glutamyl transferase levels; inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, were markedly increased. A 24-h urine collection confirmed clinically significant proteinuria (protein excretion: 1.4 g/24 h), and the patient exhibited hypoalbuminemia (serum albumin: 2.0 g/dL). Blood and stool cultures, hepatitis B surface antigen, anti–hepatitis C virus antibody, cytomegalovirus viral load, and human immunodeficiency virus type 1 polymerase chain reaction (PCR) findings were all negative. A multiplex stool PCR panel for 15 enteric pathogens also detected no organisms.

Chest radiography demonstrated bilateral pleural effusions; subsequent echocardiography and computed tomography revealed a similar pattern of intestinal wall thickening and pseudo–gastric outlet obstruction. Additionally, bilateral hydronephrosis and a pericardial effusion measuring 1.5 cm in thickness were identified (Figure 1F). No thrombosis or intestinal infarction was observed.

Brain magnetic resonance imaging and contrast-enhanced computed tomography revealed generalized cerebral atrophy without evidence of vasculitis, infarction, or venous thrombosis. Cerebrospinal fluid analysis demonstrated mildly elevated protein levels with normal glucose concentration and cell counts. Cerebrospinal fluid culture, viral PCR, TB PCR, and autoimmune panel findings were negative.

CLINICAL COURSE:

After the patient’s condition had been stabilized, upper and lower endoscopy with biopsy were performed. Endoscopic evaluation revealed diffuse mucosal edema throughout the gastrointestinal tract. Histopathologic examination demonstrated chronic nonspecific gastritis, ileitis, and colitis without granulomas or dysplasia (Figure 2). Although the patient was maintained on strict nil per os status for several weeks to monitor chronic mucus-bloody diarrhea, her symptoms did not improve. Subsequent immunologic studies revealed a high antinuclear antibody titer of 1: 1280 with a homogeneous pattern; positive anti–double-stranded DNA (anti-dsDNA), anti-histone, and anti-nucleosome antibody findings; and considerably reduced complement levels. Pleural fluid analysis demonstrated exudative effusion with a positive antinuclear antibody titer of 1: 80. Based on these findings, infectious etiologies were excluded, and meropenem was discontinued. A summary of key laboratory data is provided in Table 2 and Figure 3. A definitive diagnosis of SLE with multiorgan involvement was established, including lupus enteritis, lupus nephritis, autoimmune hemolytic anemia with pancytopenia, pleuropericardial serositis, and neuropsychiatric lupus. The SLE Disease Activity Index score was 44, indicating high disease activity. The patient received intravenous methylprednisolone at 1 g daily for 3 consecutive days, followed by intravenous dexamethasone at 5 mg every 6 h. After 2 weeks of high-dose corticosteroid therapy, gastrointestinal symptoms, fever, and dyspnea substantially improved. Considering the presence of renal and neurologic involvement, induction therapy with intravenous cyclophosphamide was initiated every 3 weeks for 6 doses, in combination with oral hydroxychloroquine 200 mg daily and isoniazid prophylaxis. She was discharged on tapering oral corticosteroids and mycophenolate mofetil for maintenance therapy. At the 3-month follow-up, SLE was well controlled. Psychosis, dyspnea, and lower-extremity edema had resolved. Laboratory evaluation demonstrated normalization of hematologic indices, complement levels (C3 and C4), and urinalysis, with complete resolution of proteinuria (Table 3).

Discussion

This case highlights the importance of recognizing atypical gastrointestinal manifestations of SLE, particularly when clinical presentation deviates from classical disease features. The patient initially presented with subacute high-grade fever, mucus-bloody diarrhea, and generalized abdominal pain, which led to an initial misdiagnosis of infectious gastroenteritis and thalassemia. Lack of response to antimicrobial therapy and progressive systemic involvement, including acute hemolytic anemia, pleuropericardial effusion, and subsequent neuropsychiatric manifestations, raised suspicion of an underlying systemic autoimmune disorder. Subsequent immunologic testing confirmed the diagnosis of SLE according to the 2019 and updated 2023 EULAR/ACR classification criteria [4,5].

In our patient, the disease process likely began earlier, as evidenced by substantial weight loss and anemia that had progressed for several weeks before diagnosis. These findings suggest that autoimmune activity was present but unrecognized during the early disease course. Although initial neurological examination findings were unremarkable, neuropsychiatric manifestations developed during hospitalization, including behavioral changes, confusion, and seizure activity. Brain magnetic resonance imaging demonstrated generalized cerebral atrophy, which was interpreted as a chronic sequela of prolonged disease activity rather than evidence of acute inflammation.

The primary diagnostic challenge was the absence of typical mucocutaneous features and the presence of uncommon gastrointestinal symptoms at presentation. Although the patient fulfilled multiple SLE classification criteria – including fever, leukopenia, thrombocytopenia, autoimmune hemolysis, seizures, serositis, proteinuria, positive antinuclear antibody findings, anti-dsDNA antibodies, and hypocomplementemia – chronic mucus-bloody diarrhea represented an atypical manifestation. Such presentations may lead clinicians toward infectious etiologies or inflammatory bowel disease, resulting in diagnostic delay, unnecessary investigations, or inappropriate treatment.

Immunosuppressive therapy remains the cornerstone of SLE management; however, initiation requires careful exclusion of infectious causes. This consideration is particularly important in endemic regions such as Thailand and other Asian countries, where TB and enteric infections may closely mimic autoimmune disease [21,22]. Our patient underwent extensive evaluation to exclude infectious etiologies, including Clostridioides difficile, gram-negative enteropathogens, and mycobacterial infection, all of which yielded negative results. After infection had been ruled out, immunosuppressive therapy was initiated safely and effectively.

The differential diagnosis of chronic diarrhea in SLE includes protein-losing enteropathy, lupus enteritis, and – rarely – VMDS. Whereas protein-losing enteropathy commonly presents with hypoalbuminemia and non-bloody diarrhea, our patient exhibited persistent mucus-bloody diarrhea, suggesting a vasculitic process rather than intestinal lymphangiectasia [23–25]. Endoscopic findings of diffuse mucosal edema and bowel wall thickening were consistent with lupus mesenteric vasculitis [26]. Most reported cases of SLE-related enteritis involve watery or loose stools [27,28]; chronic bloody diarrhea has not previously been described as an initial manifestation.

VMDS is a rare but increasingly recognized manifestation of SLE, characterized by impaired visceral smooth muscle motility and often associated with ureterohydronephrosis or intestinal pseudo-obstruction [12–20]. Clinical presentation typically includes abdominal distention, pain, vomiting, constipation, or non-bloody diarrhea. Only a few cases have been identified at the time of SLE diagnosis; no reports have described persistent mucus-bloody diarrhea as the presenting feature [18]. Imaging findings in our patient, including diffuse bowel wall thickening, ascites, and hydronephrosis, were compatible with VMDS, supporting a diagnosis of lupus enteritis with visceral dysmotility overlap.

Although the exact pathophysiology remains unclear, immune complex–mediated vasculitis and visceral smooth muscle injury leading to impaired motility have been proposed as underlying mechanisms of VMDS and lupus enteritis [15,16,29]. Overlap between these entities may result in severe intestinal dysmotility and pseudo-obstruction. If left untreated, complications such as ischemia, infarction, or bowel perforation may occur.

Prompt recognition and treatment are essential to prevent irreversible organ damage. High-dose corticosteroids remain first-line therapy, with additional immunosuppressive agents indicated for refractory or multisystem disease. In the present case, gastrointestinal symptoms resolved after intravenous methylprednisolone, followed by cyclophosphamide induction and maintenance therapy with hydroxychloroquine and mycophenolate mofetil. Given the coexistence of lupus nephritis and neuropsychiatric lupus, intensive immunosuppressive therapy was warranted. This approach resulted in a favorable outcome without disease relapse.

According to previous studies, the treatment of choice for VMDS consists of high-dose intravenous corticosteroids, immunosuppressive agents, and supportive measures. Early diagnosis and timely initiation of therapy are necessary for recovery of visceral motility. In patients with SLE, intestinal pseudo-obstruction and ureterohydronephrosis show an excellent response to early optimal corticosteroid treatment [17]. Our patient’s recovery without relapse or surgical intervention highlights the effectiveness of early aggressive immunosuppression combined with supportive management, including bowel rest and nasogastric decompression [15].

This case adds to the limited literature describing VMDS with chronic mucus-bloody diarrhea as the initial manifestation of SLE. It emphasizes that lupus enteritis and visceral dysmotility may present atypically and that recognition of these rare features is essential for timely diagnosis and improved clinical outcomes.

Conclusions

VMDS is a rare initial gastrointestinal manifestation and a substantial diagnostic challenge in SLE. It may mimic more common conditions, such as infectious enteritis or inflammatory bowel disease, leading to delays in appropriate diagnosis and management. Clinicians should consider SLE in patients with unexplained chronic mucus-bloody enteropathy, given that early recognition of atypical presentations is essential for timely treatment and the prevention of irreversible organ damage and life-threatening complications.