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Henoch-Schönlein purpura in pediatrics: Ten years of experience at a moderate risk office of a general hospital

Received: 1-30-2019 Accepted: 8-11-2019 ABSTRACT Introduction. Henoch-Schönlein purpura (HSP) is the most common small vessel leukocytoclastic vasculitis during childhood. It is characterized by palpable purpura and/or joint, abdominal or renal involvement. Objective. To describe the epidemiological, clinical, laboratory, and evolutionary characteristics of patients with HSP. Population and methods. Observational, descriptive, and retrospective study. Patients younger than 15 years who met the Ankara criteria for HSP diagnosis were included in the period between 1/1/2008 and 12/31/2017. Results. A total of 339 patients with HSP were included; the male/female distribution was similar; their average age at onset was 7.02 years (± 3.02). The typical form was observed in 78 % and the atypical form, in 22 %, with joint involvement prior to purpura onset. Joint manifestations: 82 %; abdominal involvement: 54 %; renal manifestations: 19 %. Among patients with renal involvement, 68 % experienced it in the first month after onset. The most common symptom was isolated hematuria, and 22 % of patients with renal involvement had moderate to severe nephritis. Recurrences were observed in 15 % of patients. Conclusion. Joint manifestations were more common than what has been described in other series, whereas renal involvement was less common. Although it usually occurs in the first months of disease onset, it is worth noting that these patients need follow-up with urinary and blood pressure controls as part of their pediatric assessment.


INTRODUCTION
Henoch-Schönlein purpura (HSP) is the most common small vessel leukocytoclastic vasculitis during childhood. [1][2][3][4][5] Its incidence varies depending on geographic areas. It ranges from 10 to 20/100 000 individuals younger than 17 years per year. The average age at onset is 6 years old. According to most publications, HSP is predominant among males (2:1 ratio) and occurs most commonly during the fall and winter. [1][2][3]4,6 It is characterized by palpable purpura (this condition must always be present) and joint, abdominal or renal involvement. 1,4 It may rarely affect other organs, including the brain, lungs, heart, eyes, testicles, among others, because it is a systemic disease. 7-10 HSP is a selflimited and benign condition; it resolves spontaneously over 2 weeks in one third of cases, over 2-4 weeks in another third; and over more than 4 weeks in the rest. 2,9,[11][12][13][14] Long-term prognosis is related to renal involvement.

OBJECTIVE
To describe the epidemiological, clinical, laboratory, and evolutionary characteristics of patients with HSP. To analyze the risk factors associated with renal involvement and recurrence. the 2008 Ankara Consensus Conference criteria seen at the site from disease onset.

Exclusion criteria
Diagnosis of other prior rheumatic, immune, hematological or renal diseases or current treatment with drugs that may cause purpura. Patients with less than 2 weeks of follow-up since onset.

Statistical analysis
Continuous outcome measures were described as measures of central tendency and dispersion based on sample distribution. Categorical outcome measures were stated as absolute frequency and percentage. The χ² test or Fisher's exact test were used to study the relation among qualitative outcome measures, based on the two-way table distribution. A value of p < 0.05 was considered statistically significant. The SPSS Statistics V19 software program was used for analysis.

Ethical considerations
The protocol was reviewed and approved by the Research and Teaching Coordination and the Hospital Bioethics Committee.

RESULTS
The medical records of 339 patients were reviewed. The reasons for exclusion are detailed in
Joint manifestations were observed in 82 % of patients, with greater lower limb involvement; the most commonly affected joints were the ankles and the knees ( Table 3).

Clinical manifestations
Onset: 265 patients (78 %) presented with the typical form and 74 (22 %), the atypical presentation ( Table 2). Unusual symptoms were observed in 41 cases (   in 54 % of cases; pain was the most common symptom. Two patients had intussusception as confirmed by an ultrasound and X-rays. They had severe intestinal bleeding, whereas the remaining patients had little and intermittent bleeding. Scalp edema requiring corticosteroid treatment was observed in 8 % of patients (n = 26).
Renal involvement was detected in 65 patients (19 %). Isolated hematuria was the most common manifestation. HTN was detected in 14 patients; in all, it was part of the presentation as nephritic syndrome. Most patients (44, 68 %) had renal involvement in the first month of HSP diagnosis; while 15 (23 %), in the first 2 months. The univariate analysis showed that age (>10 years) (p = 0.004), abdominal involvement (p = 0.005), and recurrence (p = 0.000) were statistically significant factors associated with renal involvement.
Patients with moderate to severe nephritis (n = 14), defined as per the clinical criteria, were treated based on the modified protocol proposed by Niaud et al.: 3 IV pulses of methylprednisolone (1 g/1.73 m 2 ), followed by oral prednisone (30 mg/m 2 /day) for a month, then 30 mg/m 2 every other day for 2 months, and, finally, 15 mg/m 2 every other day for 15 days ( Table 3). Cyclophosphamide was indicated at a dose of 2 mg/kg/day for 2 months in patients who did not respond to corticosteroids. Total response, defined as normal proteinuria and glomerular filtration rate, was observed in 8 patients; 4 patients had partial response (residual, nonnephrotic proteinuria) with a normal glomerular filtration rate. Two patients did not respond to treatment (persistent nephrotic-range proteinuria and/or no recovery of glomerular filtration rate). Of the 2 patients who did not respond to corticosteroids, 1 showed total response to cyclophosphamide and the other had residual proteinuria. A renal biopsy was done in 8 patients, and the most common histopathological finding was focal mesangial proliferation (III.a according to the International Study of Kidney Disease in Children [ISKDC] classification). 18 Patients with persistent, non-nephrotic proteinuria received angiotensin II-converting enzyme inhibitors (n = 24).
Recurrence: One or more recurrences occurred in 52 patients (15 %). The median time since the onset of HSP until recurrence was 65 days (r = 30-540). The most common clinical manifestation of recurrence was isolated purpura (27, 52 %), whereas the rest had purpura accompanied with other type of involvement. The outcome measures associated with recurrence in this series were abdominal involvement (p = 0.006) and renal involvement (p = 0.000).
Hospitalization: A total of 63 patients (19 %) required hospitalization. The reasons for it are described in Table 4.

DISCUSSION
For this review of a ten-year experience at the moderate risk office of a public hospital, 339 patients diagnosed with HSP (as per the Ankara criteria) were registered. Patients' age at onset was similar to that reported by different authors. It has been confirmed that, although HSP may occur at any age, it is more common among school-age children. No differences were noted in terms of sex. This is different from other series that have reported a higher prevalence among males. 3,18 Seasonal distribution was observed to be similar. [2][3][4]19 In those studies, HSP usually occurs in the fall and winter. More than 80 % of patients had upper airway conditions. Although the cause of seasonal distribution is unknown, it is probably related to the action of triggering factors, such as infectious agents.
I n a l l c a s e s , t h e p r e s e n c e o f p u r p u r a (diagnostic criterion) was confirmed. Although it is typically present since the onset, "atypical" forms of HSP have been described with other signs and symptoms that develop prior to skin lesions. These forms have been described in 15 % of participants in a series of 430 children aged 2-14 years in Turkey 2 and in 25 % of participants in another study done in Italy (n = 150). 3 In our study, 22% of subjects started, in general, with joint involvement.
Besides skin involvement, HSP typically affects several other organs. Joint and abdominal manifestations have been reported as the second and third most common clinical manifestations, but their prevalence varies depending on the publication. Abdominal pain has been assessed in different studies and ranges from 35 to 50 % of patients; whereas joint involvement varies from 45 to 75 %. 2,3,17,19 Abdominal involvement was recorded in half of children seen due to this condition in the 10-year study period. Abdominal pain was the main symptom, followed, to a lesser extent, by gastrointestinal bleeding. Intussusception has been reported as an uncommon complication (1 %), which has been consistent with our findings (2 patients). Although gastrointestinal bleeding in these cases was severe, their clinical course was favorable.
In our study, the incidence of joint involvement was higher than what has been described in the bibliography. This information may have been overestimated due to the retrospective nature of data collection from medical records. Consistent with other publications, joint involvement more commonly affects the lower limbs.
The clinical course of patients with HSP is mostly favorable. Morbidity in the acute stage and the need for hospitalization are mainly related to abdominal and/or joint involvement. Long-term morbidity is related to the extent of renal involvement. 20 According to different studies, its incidence ranges from 10 to 60 %. 2,3,17,19 In this study, renal alterations were observed in 19 % of patients, and in more than 80 % of these, manifestations started within 2 months after onset. This is consistent with other reports, 3,19 but the frequency has been lower than that reported by other authors. 2,3,17,19 The median follow-up duration in our study was 75 days, but almost 30 % of patients withdrew from followup; therefore, renal alterations, which may occur in the long term, may have been underestimated. Consistent with other studies, hematuria was the most common finding. 2,3,19 Among patients with renal involvement, 22 % had moderate to severe nephritis. The series described here used the modified protocol proposed by Niaudet, based on clinical criteria. There is still controversy in relation to the management of these patients.
Different factors have been related to a higher risk for renal involvement: 21 age older than 10 years, presence of abdominal involvement, persistent purpura, and laboratory alterations ( l e u k o c y t o s i s , i n c r e a s e d p l a t e l e t c o u n t , antistreptolysin O [ASO], reduced C3 and C4). The series described here found an association with age (>10 years old), abdominal involvement, and recurrence.
The latter have been mentioned in several publications, with a frequency that ranges from 7 % in Turkey, 15 % in Spain, 33 % in the USA, to 35 % in Italy. 3,18,19,22 In our series, recurrences were detected in 15 % of cases, with a median of 65 days until onset.
Lab tests are not used to diagnose HSP. Our data shows a leukocytosis rate of 13.3 %, lower to what has been reported. 2,3 The literature includes mentions to high IgA levels between 20 and 50 %. 23 Although routine IgA levels were not tested in the patients of this study, among those who had IgA results, 9 5% showed high levels.
A weakness of this study was the lack of long-term evolutionary data. On the one side, follow-up duration may have been affected by the dropout rate (approximately 30 % of patients) and, on the other, by the subsequent changes in the follow-up protocol. In recent years, follow-up duration has extended due to the importance of continued monitoring of renal involvement after the acute stage.
The prognosis of patients with HSP is generally very good; in the absence of significant renal involvement, most patients recover in the first month after onset. Most patients with renal involvement develop it in the first 2 months (90 %), and 97 %, within 6 months. 20 However, follow-up should continue for a year after initial onset. In the first 2 months, the recommendation is to control patients' blood pressure and urine analysis results every week, and then to space controls to once a month or every 2 months. Considering the potential for late manifestations, urine analysis and blood pressure should be monitored yearly as part of the routine pediatric assessment in children with a history of HSP.
Renal function should be monitored in children with abnormal urine tests; those with persistent proteinuria, HTN or renal failure should be assessed by a pediatric nephrologist. Pregnant women with a history of HSP should be monitored due to their higher risk for HTN. 24 n