Introduction: Schönlein-Henoch disease is a small vessel vasculitis resulting from IgA-mediated inflammation. It is the most common acute systemic vasculitis in childhood, mainly affecting the skin, gastrointestinal tract, joints, and kidneys. Although the prognosis of Schönlein-Henoch is generally good, gastrointestinal tract involvement is a potential complication, presenting as massive gastrointestinal bleeding, bowel infarction, perforation, as well as intussusception and peritonitis.

Aim: In everyday clinical practice, determining markers of gastrointestinal tract involvement is critical when the initial or only available symptoms are related to it. Ultrasound diagnosis is effective as a first-line screening method in children with Schönlein-Henoch purpura and abdominal involvement, in order to objectivize changes in the small intestinal wall, such as thickening, disturbance of its stratification, and intramural bleeding.

Materials and methods: Since, until recently, the generally accepted concept that there are neither coagulation disorders nor changes in the small intestinal wall’s ultrasound examination has limited our understanding of the essence of Schönlein-Henoch disease, we looked for more trustworthy indicators.

Results: These indicators, such as factor XIII and von Willebrand factor-associated antigen, showed significant deviations from the reference ranges in our study of patients with abdominal pain who had Schönlein-Henoch disease.

Conclusions: In conclusion, early assessment of altered coagulation factors f. XIII and vWF:Ag and ultrasound monitoring of changes in the small bowel wall proved to be a valid criterion for therapeutic accuracy as well as avoiding surgical complications.

abdominal pain, factor XIII, Schönlein-Henoch purpura, ultrasound, Von Willebrand associated antigen (vWF:Ag)

Schönlein-Henoch disease is a small vessel vasculitis resulting from IgA-mediated inflammation. It is the most common acute systemic vasculitis in childhood affecting mainly the skin, gastrointestinal tract, joints, and kidneys. The main clinical presentation is purpura without thrombocytopenia characterized by a bilaterally symmetrical distribution of both lower extremities, abdominal pain, arthralgia, blood in the stool, hematuria, and/or proteinuria.^{[1, 2]} An increased production of polymeric IgA by the immune system in response to mucosal-presented antigens, such as bacteria, viruses, or fungi, is thought to be the underlying mechanism. The concentrations of pro-inflammatory cytokines, which induce endothelial damage, rise during the acute phase of the disease. Schönlein-Henoch purpura is usually a disease of children between the ages of 3 and 10 years, with 50% of all cases occurring at or before the age of 5 years.^{[3, 4]} Although the prognosis of Schönlein-Henoch is generally good, gastrointestinal tract involvement is a potential complication, presenting as massive gastrointestinal bleeding, bowel infarction, perforation, as well as intussusception and peritonitis. In fact, surgical interventions related to gastrointestinal complications are performed in 5%–12% of patients with the syndrome, and for recurrences, this percentage is reported to be as high as 30%.^[5] In everyday clinical practice, determining markers of gastrointestinal tract involvement when the first or only available symptoms are related to it is critical in order to avoid invasive procedures such as endoscopy or laparotomy.

We set out to identify biochemical and immunological markers that indicate gastrointestinal involvement in Schönlein-Henoch disease, as well as to monitor ultrasound changes in the small intestinal wall, in order to refine therapeutic behavior and reduce the need for invasive surgical procedures.

1. Determination of the levels of von Willebrand factor-associated antigen (vWF:Ag)

2. Determination of the levels of factor XIII

3. Ultrasonographic findings in small intestinal wall

Ultrasound examinations in patients with abdominal form of Schönlein-Henoch disease were performed with HITACHI ARIETTA 70 and VINNO 5 ultrasound machines, with linear transducers with a frequency of 5-9 MHz. Standard settings during the study included increased platelet rich fibrin (PRF) and total gain levels. At default settings, only the normal structure of the intestinal wall is visualized during the examination. The ultrasound examination was conducted in the morning on an empty stomach, and at the beginning of the examination, the relevant patient took 50 ml of water in order to better visualize the internal hypoechoic layers of the intestinal wall of the small intestine - the lamina propria. Additionally, the power Doppler signal between the individual layers was evaluated for accurate assessment of mucosal damage.

4. Statistical methods used: descriptive statistics, Kolmogorov-Smirnov test, tests for related and unrelated samples (Student t-test, and Pearson’s correlation coefficient)

In a retrospective study conducted between 2015 and 2018, 54 children with Schönlein-Henoch disease were diagnosed, monitored, and followed up. During 2019-2023, a prospective observation was conducted, including a change in the current approach for diagnostic-therapeutic refinement, of 15 patients with the same nosological unit.

The percentage distribution of the disease forms from the retrospectively observed cases is presented in Fig. 1, which shows that the abdominal manifestation is commonly associated with the skin and joint form (23%).

Figure 1.

Distribution of the forms of the disease in percentages.

It has been established that the inflammatory and coagulation systems have a bidirectional interaction. Results from the standard coagulation tests in Schönlein-Henoch purpura, even in the acute phase, show that PT, aPTT, and fibrinogen are within normal ranges and cannot be reliable predictors of the onset and severity of abdominal involvement in Schönlein-Henoch disease. The changes in the D-dimer levels, regardless of certain deviations from the reference values in the course of intense abdominal pain, are also not reliable paraclinical indicators; as well as the fact that the values of IgA, C3, and C4 did not show a significant deviation from the reference ranges. An activation of the inflammation leads to activation of the coagulation system, which also markedly affects inflammatory activity. Since, until recently, the knowledge about the essence of Schönlein-Henoch disease has been reduced to the generally accepted concept that there are neither coagulation disorders nor changes in the ultrasound examination of the small intestinal wall, we searched for more reliable indicators.

Factor XIII, a fibrin-stabilizing factor, is significantly decreased during the acute phase of Schönlein-Henoch and has been suggested to be a prognostic indicator of the disease.^{[6, 7]} Von Willebrand factor can also be used as a specific marker of vascular damage and disease activity in Schönlein-Henoch purpura. vWF:Ag has been found to be a marker of vascular damage rather than an acute-phase reactant. Elevated vWF:Ag values reflect the increased amount of factor released into the circulation from the endothelium due to the ongoing vascular damage. Values return to normal when patients are in remission and remain above normal levels when symptoms persist. Assessment of vWF and RiCOF can be accepted as reliable tests for monitoring the disease activity.

Most cases of Schönlein-Henoch disease with severe abdominal pain have so far been treated with low-dose steroids, without clear criteria for treatment initiation, dose regimen, and duration.

In the conducted prospective study, we included 15 patients in the age range of 4-17 years (median age 11), with no statistically significant differences between the sexes. The percentage distribution of the clinical forms of the disease is shown in Fig. 2, from which it could be concluded that the abdominal manifestation is usually associated with skin and joint form.

Figure 2.

Distribution of Schönlein-Henoch disease form (%) for patients (n=15).

In 5 of all 15 patients, the vWF:Ag was found to be abnormal according to the blood type. Of these five patients, 4 were with abdominal involvement; moreover, 3 of them had a disturbed stratification of the small intestinal wall (Fig. 3).

Figure 3.

Distribution of the patients (n=15) according to vWF:Ag values.

Four of the 15 children whose factor XIII values were evaluated showed abnormal results: two had abdominal pain and the ultrasound revealed small intestinal involvement, and three had values below the reference range.

Abnormal factor XIII levels, abdominal pain, impaired stratification and preserved thickness of the small intestinal wall were found in one patient (Fig. 4).

Figure 4.

Distribution of patients (n=15) by factor XIII values.

Furthermore, abnormal values of both factors were found in only two patients (one of them with abdominal involvement).

Ultrasound diagnosis has been established to be effective as a first-line screening method in children with gastrointestinal symptoms of the disease.^[8] The normal intestinal wall consists of five layers, including the outermost echogenic thin mucosal and serous surface layers with a submucosa that appears as a continuous homogeneous echogenic structure less than 2 mm thick, delineated by two hypoechoic layers: the inner-lamina propria and external-muscularis propria.^[9] Using a high-resolution ultrasound, the changes in the intestinal walls can be demonstrated in three grades. Ultrasonography can help rule out acute surgical abdomen and establish a correct diagnosis, even in the absence of typical skin lesions.^[10]

Ultrasound examination in a patient presenting with severe abdominal pain: three of the available five sonographically visible layers of the small bowel wall were available for measurement, with a total wall thickness of 4.1 mm–4.8 mm, accompanied by dilatation in the total diameter of the small bowel loop (outer diameter of lumens 13-16 mm) (Fig. 5).

Figure 5.

Abdominal ultrasound of a patient with severe abdominal pain and Schönlein-Henoch purpura.

In another clinical case, we observed slightly dilated small intestinal loops (67 mm) with a non-thickened wall (1.6-1.8 mm), with disturbed stratification (three of the five layers of the small intestinal wall described sonographically were visible); the presence of a color Doppler signal between its separate layers was visualized (Fig. 6).

Figure 6.

Ultrasonographic findings in a patient with abdominal form of Schönlein-Henoch disease (presence of a color Doppler signal between its separate layers was visualized).

During an ultrasound examination of another patient with the abdominal form of Schönlein-Henoch disease, impaired stratification of the small intestinal wall was visualized with preserved thickness. Additionally, in the ileocecal region, a ‘target’ symptom was visualized, an appendix with swollen, thickened walls, and a small amount of peri-appendicular effusion (Fig. 7).

Figure 7.

Abdominal ultrasound in a patient with abdominal pain with Schönlein-Henoch disease: disturbed stratification of the small intestinal wall and swollen appendix with peri-appendicular fluid.

Ultrasound examination is a useful method in the monitoring and follow-ups of patients with Schönlein-Henoch disease, in conjunction with the laboratory tests presented in Table 1.^[10]

Age beyond 7 years was related with a 6.4 times larger chance of recurrence, according to the findings of a pooled sample of 69 children (retrospective and prospective analysis) (p=0.0235).

The abdominal form is six times more common in children older than 4 years. The abdominal form was more than six times less common in children in whom the trunk was not affected by the rash and more than 17 times more likely in patients with ultrasound findings of disturbed stratification of small intestinal wall.

The need to specify the nature of the abdominal pain and the determination of the beginning, duration, and dosage regimen of the administered corticosteroid treatment should be based on the determination of the levels of vWF:Ag and factor XIII, in parallel with the monitoring of the sonographic changes: thickening, change in the stratification of the small intestinal wall, and the presence of a color Doppler signal.

Despite many years of research into Schönlein-Henoch disease, and contrary to the widely held belief that there is nothing more to learn about this condition, the findings of our study challenge this belief. Furthermore, there are still unclosed niches in terms of diagnostic refinement and therapeutic approach. When these gaps are filled, we anticipate there will be a significant reduction in the incidence of serious surgical complications, which are now reported in the literature to be 5-12% of patients with the syndrome, with recurrence rates as high as 30%.^[5]

1. The clinical manifestation of Schönlein-Henoch’s vasculitis in recent years goes beyond the definition of “benign disease” and even in cases with an isolated skin form, there is a tendency for repeatability and aggressiveness of the urticarial-hemorrhagic rash (especially after the appearance of COVID-19 infection).

2. The levels of vWF:Ag and factor XIII change most distinctly when the abdominal form of the disease appears.

2.1. Ultrasound diagnosis of the small intestinal wall has been shown to be effective as a first-line screening method in children with abdominal involvement of Schönlein-Henoch purpura.

2.2. Ultrasonographic findings can help identify changes in the small intestinal wall even in the absence of typical skin lesions and can help rule out an acute surgical abdomen.

2.3. Serial ultrasonography makes it possible to account for the progressive reduction of the thickening of the small intestinal wall, the reappearance of peristalsis and visualization of the small intestinal folds. When there is a disturbed stratification of the small intestinal wall (its five layers are not clearly demarcated), despite preserved normal thickness of the small intestinal wall, there are indications for the initiation of corticosteroid therapy.

3. Early assessment of the altered coagulation factors f. XIII and vWF:Ag and ultrasound monitoring of changes in the small bowel wall proved to be a valid criterion for avoiding surgical complications in none of the observed patients from the prospective group.

3.1. Corticosteroid treatment in severe abdominal forms was conducted in parallel with monitoring the echographic changes in the stratification and thickness of the small intestinal wall. In case of persistence of clinical symptoms and unsatisfactory reverse dynamics in echographic changes of the small bowel wall, treatment can be continued with a dose reduction of 25% per week lasting up to 4 weeks, based on the study by Lei et al.^[11]

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The authors have declared that no competing interests exist.