IgA-Associated Vasculitis Presenting With Acute Abdominal Syndrome in an Older Patient

Introduction

IgA-associated vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is a rare disease with an annual incidence of 0.1 to 14 per 100 000. IgAV is the most common cause of systemic vasculitis in children; its annual incidence in adults is approximately 0.8 to 2.2 cases per 100 000. Although much less common in adults, IgAV is more frequently associated with increased disease severity [1]. IgAV shares a similar pathogenesis but has distinct clinical manifestations relative to IgA-associated nephritis [2]. Due to the limited number of clinical studies, no specific treatment regimens or clear diagnostic and therapeutic guidelines for IgAV have been established.

Sudden abdominal pain and bloody diarrhea are among the most common manifestations of IgAV in children. In many cases, abdominal symptoms are triggered by a respiratory tract infection. The clinical presentation of IgAV is often associated with involvement of multiple organs, including the kidneys [3]. During the courses of IgAV and IgA-associated nephritis, pathological deposits of immunoglobulin A are localized in the glomeruli. A small proportion of the population might have a genetic susceptibility to IgAV: individuals with abnormalities in O-glycan biosynthesis have a higher frequency of galactose-deficient-IgA1 (Gd-IgA1)-anti-glycan-IgG immune complex deposits in the mesangium, leading to inflammation and cellular proliferation [3]. This abnormality may be associated with an increased circulating IgA concentration and the presence of genetic polymorphisms in hypervariable regions of these proteins [3].

Typical renal manifestations of the disease include asymptomatic hematuria and non-nephrotic proteinuria, which are often detected incidentally during routine urinalysis. Over time, progressive glomerular inflammation may lead to a gradual decline in estimated glomerular filtration rate. Diagnosis is commonly based on the detection of intrarenal mesangial or vascular IgA deposits by immunofluorescence or immunohistochemical examination of a kidney biopsy [4], and – when appropriate – by skin biopsy of a suspicious lesion [1], along with the presence of erythrocyte casts or dysmorphic red blood cells in urine sediment [4]. Treatment for IgAV, particularly in cases with persistent proteinuria or declining kidney function, includes oral corticosteroids and conventional immunosuppressive agents [5]. However, there is no solid evidence that these therapies effectively prevent nephropathy onset or progression in patients with IgAV [6].

This report describes an older man with IgAV. The clinical manifestations of the disease were typical, but the patient’s advanced age and comorbidities made the final diagnosis unexpected.

Case Report

A 67-year-old central European man was admitted to the diabetology department due to poor control of type 2 diabetes and worsening diabetic vascular complications, including diabetic foot. Additionally, the patient had several comorbidities, including treatment-resistant arterial hypertension, hyperlipidemia, bilateral cataracts, and diabetic retinopathy.

One week before admission, a blister filled with purulent discharge had been observed on the patient’s left big toe. Blood glucose self-monitoring at home indicated poor glycemic control, with levels reaching 26.1 mmol/L. At admission, laboratory tests showed an elevated C-reactive protein level (122.4 mg/L) and hyperglycemia (fasting glucose 15.7 mmol/L). No clinically significant acid-base abnormalities were noted. Mild normocytic anemia was present (Table 1).

During hospitalization, the wound on the patient’s foot was surgically cleaned and dressed; glycemic control was improved with intensified insulin therapy. On the sixth day of hospitalization, a fine, bright red, spotted rash appeared on the patient’s calves (Figure 1). Further physical examination of the affected skin showed that the macules were non-palpable and did not blanch under pressure. At this stage, the cause of the rash was unclear; therefore, a biopsy of a skin lesion was performed. Histopathological examination yielded inconclusive results. Although weak, finely granular IgA deposits were observed within the arteriolar walls, these findings did not fulfill the diagnostic criteria for a definitive diagnosis of IgAV. No clear signs of vascular inflammation were observed in the skin specimen. As part of the diagnostic evaluation, a kidney biopsy was performed. Among 9 glomeruli in the sample, 1 showed sclerosis. Mesangial cell proliferation and increased mesangial matrix were observed, along with segmental thickening of capillary walls and sclerosis. Mesangial IgA staining was detected in 4 glomeruli. Electron microscopy confirmed findings consistent with IgA nephropathy and concurrent diabetic kidney disease.

The next day, the patient began reporting intense acute pain in the mid-abdomen, accompanied by nausea and loss of appetite. These symptoms rapidly worsened. Physical examination revealed increased muscular guarding upon palpation of the right lower abdomen. Ultrasonographic examination initially suggested acute appendicitis. Because of the patient’s worsening general condition and the urgency of the situation, immediate surgical management was chosen to avoid potential delays associated with additional imaging. During the surgical intervention, a different diagnosis emerged. The abdominal symptoms were not caused by appendicitis; they originated from acute venous ischemia of the small intestine, with areas of necrosis and chemical peritonitis. Accordingly, the procedure was changed to an ileocecal resection. A stoma was subsequently created on the right side of the lower abdomen. Antimicrobial therapy with ciprofloxacin and metronidazole was initiated after the operation, considering the presence of intestinal necrosis.

During the procedure, tissue samples were collected, including a specimen of the ischemic small intestine and a sample of ileum with appendix. Pathological examination showed a hyperemic mucous membrane with fibrin, blood, and numerous neutrophils in both samples. The appendix specimen showed no evidence of inflammation. A decrease in glomerular filtration rate was observed both before and after the surgical intervention (Figure 2). Concurrently, the patient’s skin lesions resolved. He was discharged after 18 days in overall stable general condition.

Two weeks later, the patient was re-admitted to the hospital emergency department with persistent general weakness and nausea (Figure 3). Laboratory tests revealed typical biochemical features of acute kidney injury accompanied by oliguria. Serum creatinine and urea levels increased to 381.7 μmol/L and 37.1 mmol/L, respectively. Furthermore, hyponatremia (sodium 126.8 mmol/L), hyperkalemia (potassium 6.74 mmol/L), and compensated metabolic acidosis were present (Table 2). Disseminated red macules remained visible on the patient’s skin, although they were less pronounced than during the previous hospitalization. Due to his impaired renal function, the patient was transferred to the nephrology ward. At that time, he was weak and hypotensive, which led to the administration of a continuous norepinephrine infusion. Blood-borne infection was excluded based on negative microbiological culture findings. Intensive intravenous fluid therapy and broad-spectrum antibiotic treatment with ceftriaxone and ciprofloxacin were administered. Considering the unsatisfactory correction of electrolyte imbalance and a rapid decline in estimated glomerular filtration rate to 13 mL/min/1.73 m2, hemodialysis was initiated. Only 1 hemodialysis session was required; urine output quickly increased, and serum creatinine decreased to 101 μmol/L by 3 days after the session. Urinalysis revealed subnephrotic proteinuria (1.26 g/L) and dysmorphic red blood cells. In conjunction with the presence of multiple skin lesions on the patient’s upper and lower limbs, the urinalysis findings led to suspicion of glomerular disease. A kidney biopsy was performed, and pathological examination confirmed the coexistence of IgAV and diabetic nephropathy. Because kidney function remained stable (serum creatinine 92.1 μmol/L, serum urea 6.1 mmol/L) and urine output was normal, corticosteroid therapy was not initiated. The patient’s general condition gradually improved, and he was discharged after 21 days of hospitalization. The main findings at that time are summarized in Figure 3. The patient was advised to undergo nephrology follow-up monitoring. During the subsequent 6-month follow-up period, immunosuppressive therapy was not required, and no relapses were observed.

Discussion

IgAV in older patients is a rare entity that may present with a wide range of clinical manifestations. Concurrent allergy or infection may trigger an abnormal immune-mediated response. The disease course often varies in both presentation and severity; it may lead to serious complications that often depend on underlying health conditions.

Our patient was older and had a long history of poorly controlled diabetes mellitus. Male sex and diabetic status represent important risk factors for IgAV; they are considered adverse prognostic indicators [7]. Coexisting arterial hypertension and dyslipidemia may have further contributed to the patient’s severe manifestations of vasculitis and the onset of multiple complications. The diagnosis of IgAV was unexpected because this disease is most commonly diagnosed in children and adolescents, in whom it usually follows a mild course and rarely leads to serious complications [8]. Buscatti et al described a case series of 322 pediatric patients with IgAV; 11% of patients exhibited intermittent abdominal pain [9]. However, our patient’s advanced age and multiple comorbidities made it difficult to establish the correct diagnosis without renal biopsy. Initially, an ischemic or atherosclerotic etiology appeared to be the most probable explanation for the acute abdomen. The deposition of IgA in vascular walls may have resulted in ischemia and consequently led to ileal necrosis. Therefore, an association between IgAV and ileal necrosis was suspected. However, the absence of IgA staining in the resected necrotic ileum specimen precluded definitive histopathological confirmation.

The diagnosis of abdominal IgAV with concurrent renal involvement is commonly associated with a poor prognosis. Older patients are particularly susceptible to severe gastrointestinal manifestations of IgAV, which are strongly associated with an increased risk of progression to end-stage renal disease [10]. In the present case, transient deterioration of kidney function was observed; 1 hemodialysis session was sufficient to enable gradual improvement in renal function. In subsequent days, the serum creatinine level decreased to near-normal values, and urine output increased. Stanway et al recently reported that IgAV diagnosed in the sixth decade of life or later is much more likely to lead to end-stage kidney disease compared with the same diagnosis in younger patients [7].

Published reports describing similar cases of IgAV in older patients demonstrate the severe nature of the disease. Acute abdominal pain – often the primary symptom – is nonspecific. The classical sequential tetrad of palpable purpura, polyarticular pain, abdominal pain, and urinalysis abnormalities is rarely present on admission [11].

Although abdominal pain is among the 3 most common reasons for presentation to the emergency department [12], it is only occasionally associated with acute ischemia of the ileum. The most common vascular causes of acute abdominal syndrome are mesenteric ischemia and ruptured abdominal aortic aneurysm [13]. These conditions most frequently affect women age 60 and older. The pain is typically severe, gradually increasing over several hours, and may occur after a meal. Laboratory tests are rarely helpful in the diagnostic process. The standard diagnostic approach in cases of acute abdominal pain includes physical examination and abdominal ultrasonography [13]; in our patient, such investigations only showed slight intestinal wall thickening. Direct intraoperative assessment revealed multiple ischemic foci accompanied by peritonitis; these changes were consistent with vasculitis. Given the presence of skin purpura accompanied by acute kidney injury and the detection of red blood cells and protein in the urine, a kidney biopsy was performed. Previous laboratory tests, including antinuclear antibodies and antineutrophil cytoplasmic antibodies, yielded negative findings. Moreover, spontaneous remission of the disease was observed. After the infection had been treated, the patient’s kidney function and general condition gradually improved. The decision not to initiate immunosuppressive therapy with corticosteroids was supported by the patient’s history of poorly controlled diabetes mellitus.

The treatment of IgAV in older patients remains controversial. When deciding whether to initiate immunosuppressive therapy, clinicians should consider the possibility of spontaneous resolution, as observed in our patient despite initially severe symptoms and serious impairment of kidney function. In the present case, corticosteroid therapy was withheld. This decision did not adversely affect recovery time and helped to avoid potential treatment-related adverse effects.

Conclusions

This case demonstrates that IgAV, although predominantly a pediatric condition, should also be considered in older patients who present with acute abdominal symptoms. It underscores the diagnostic challenges encountered in this age group and highlights the potential for severe outcomes if the condition is misdiagnosed or managed inappropriately. Given that advanced age and diabetes are both associated with worse renal prognosis and increased systemic complications, meticulous diagnostic evaluation and careful clinical monitoring remain essential in such patients.