Cerebral vasculitis in a case of henoch–Schönlein purpura: An unusual presentation

Indrasish Ray Chaudhuri; Vikram Bhaskar; Anju Aggarwal; Sonal Sharma

doi:10.4103/ipcares.ipcares_10_21

CASE REPORT

Year : 2021 | Volume : 1 | Issue : 1 | Page : 10-13

Cerebral vasculitis in a case of henoch–Schönlein purpura: An unusual presentation

Indrasish Ray Chaudhuri¹, Vikram Bhaskar¹, Anju Aggarwal¹, Sonal Sharma²
¹ Department of Pediatrics, University College of Medical Sciences and Associated Guru Teg Bahadur Hospital, Delhi, India
² Department of Pathology, University College of Medical Sciences and Associated Guru Teg Bahadur Hospital, Delhi, India

Date of Submission	08-Oct-2020
Date of Decision	15-Oct-2020
Date of Acceptance	04-Nov-2021
Date of Web Publication	27-Feb-2021

Correspondence Address:
Dr. Vikram Bhaskar
Room No. 602, Department of Pediatrics, MCH 6th Floor, University College of Medical Sciences and associated Guru Teg Bahadur Hospital, Delhi
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_10_21

Abstract

Background: Henoch–Schönlein purpura (HSP) is the most common vasculitis seen in children that rarely involve central nervous system (CNS) (0.65%–8%). Patients with CNS vasculitis may present with symptoms such as headache, seizures, focal neurological deficit, or behavior abnormalities. We describe a case of HSP where the patient presented with developmental delay along with skin rash and renal involvement. Clinical Description: A 15-month-old boy presented with a history of developmental delay and skin rashes for the past 2 months. There was no significant antenatal or birth history. At the age of 15 months, the child could not sit without support, could not transfer objects from one hand to other, could only speak bisyllables, and could not wave “bye-bye.” On examination, the patient had normal vitals with equal volume peripheral pulses and normal blood pressure in all four limbs. Urine examination showed microscopic hematuria, and kidney functions were mildly deranged. Skin biopsy showed immunoglobulin A vasculitis. Magnetic resonance imaging brain was done which revealed multifocal areas of altered signal intensity in periventricular deep white matter in bilateral frontal and parieto-occipital lobes, appearing hyperintense on T2-weighted and fluid-attenuated inversion recovery sequences, showing evidence of diffusion restriction, suggestive of areas of acute ischemia. The findings were consistent with manifestations of CNS vasculitis. Management: The patient was managed conservatively and advised physiotherapy and follow-up for developmental delay. Conclusion: HSP can rarely involve CNS, however, developmental delay in HSP has never been reported before.

Keywords: Central nervous system, purpura, vasculitis

How to cite this article:
Chaudhuri IR, Bhaskar V, Aggarwal A, Sharma S. Cerebral vasculitis in a case of henoch–Schönlein purpura: An unusual presentation. Indian Pediatr Case Rep 2021;1:10-3

How to cite this URL:
Chaudhuri IR, Bhaskar V, Aggarwal A, Sharma S. Cerebral vasculitis in a case of henoch–Schönlein purpura: An unusual presentation. Indian Pediatr Case Rep [serial online] 2021 [cited 2023 Apr 1];1:10-3. Available from: http://www.ipcares.org/text.asp?2021/1/1/10/310208

Pediatric vasculitis is a complex group of conditions that involve multiple systems. Vasculitis is defined as the inflammation of the blood vessel wall. The site of vessel involvement, size of the affected vessels, extent of vascular injury, and underlying pathology determine the disease phenotype and severity. Vasculitis can be primary, where the etiology is unknown or secondary when associated with infection, malignancy, drug exposure, rheumatic conditions, i.e., systemic lupus erythematosus and juvenile dermatomyositis, and others.^[1] The annual incidence of primary vasculitis in children and adolescents younger than 17 years is approximately 23 per 100,000.^[2] Of the primary vasculitis, Henoch–Schönlein purpura (HSP), also known as immunoglobulin (Ig) A vasculitis, is the most common, accounting for 49% of all childhood vasculitis.^[2]

HSP is a systemic, small-vessel vasculitis involving the skin, joints, kidneys, and gastrointestinal with peak onset between 4 and 6 years of age.^[2] The classic presentation of HSP includes lower extremity purpura, arthritis, abdominal pain, and renal disease. Unusual manifestations such as edema of the scrotum, eyes, or hands and pulmonary hemorrhage have been reported. Central nervous system (CNS) involvement in HSP is rare (0.65%–8%) and sometimes leads to long-term neurological sequelae.^[3],[4] These patients with underlying CNS vasculitis may present with acute symptoms such as headache, seizures, focal neurological deficit, or behavior abnormalities. Garzoni et al.^[5] described the repertoires of CNS dysfunction which were altered consciousness (58%), seizures (14%), focal neurological deficits (26%), visual disturbances (24%), and speech disturbances (10%).

We report a case of a 15-month-old child with HSP and CNS vasculitis. The case is unique, as the patient did not have any acute symptoms or focal neurological deficits, but presented with a history of developmental delay.

Clinical Description

A 15-month-old boy with a history of delayed development presented to the pediatric outpatient department with generalized rashes all over the body for the past 2 months. The rashes appeared suddenly, initially involving both lower limbs, followed by gradual progression to involve the whole body over 2 months. There was no history of any fever, inexplicable bouts of crying, swelling, restricted movements of painful joints, reddish or cola-colored urine, bloody stools, lethargy, increased irritability, head banging, seizures, or history of being on any medication.

There was no history of similar rashes in the past. The antenatal history was uneventful. The baby was a normal hospital delivery at term who cried immediately after birth and weighed 2.8 kg at birth. There was no significant illness in the neonatal period requiring hospitalization. Delayed acquisition of developmental milestones became apparent at 9 months of age when the mother noticed that her child could not sit with support like his peers. Elicitation of developmental history revealed that the child attained neck holding at 3 months of age and rolling over at 7 months from supine to prone but could not sit even with support at 15 months. The child started reaching out for objects with one hand at 6 months of age but could not transfer objects from one hand to other at 15 months. The child started uttering monosyllables at 6 months of age, bisyllables at 9 months but could not speak any words with meaning at 15 months of age. The child developed social smile at 3 months and stranger anxiety at 8 months but could not wave “bye-bye.” There was no history of loss of any previously learned milestones or any apparent visual or hearing impairment. The last vaccine that the child had received was at 9 months of age. He was the product of nonconsanguineous marriage, first in birth order, and there was no family history suggestive of similar illnesses or other neurological disorders.

At admission, the child was alert and playful, vitals were normal with a heart rate of 90/min and respiratory rate of 30/min, and all peripheral pulses were palpable. Blood pressure in all four limbs was similar and <90^th centile for his age. The head circumference was 46 cm (between -1 and +1 standard deviation). Weight and length were normal for age. Clusters of small (0.5 mm) raised, erythematous, nonblanchable lesions were noted on the extensor aspect of both lower limbs suggestive of purpura. Mild pallor was present. There were no neurocutaneous markers, no facial dysmorphism, no joint swelling or tenderness, and no cranium or spine abnormality. Neurologic evaluation revealed increased tone in bilateral upper and lower limbs with brisk deep tendon reflexes and bilateral extensor plantar response. Cranial nerve examination was normal, and there was no focal neurological deficit. Rest of the systemic examination was normal. Based on the clinical findings (presence of generalized purpura), a provisional diagnosis of global developmental delay with possible HSP was kept, and further workup, including skin biopsy, was planned.

Management and Outcome

The hemogram revealed a hemoglobin of 11.5 g%, total leukocyte count of 7500/mm³, platelet count of 2.14 lakh/mm³, and elevated erythrocyte sedimentation rate of 40 mm. Coagulation studies were normal. Renal parameters comprised blood urea of 19 mg/dl, serum creatinine of 1.4 mg/dl, urine microscopy >10 red blood cells/high-power field, and urine protein/creatinine ratio of 1.2. Stool examination for occult blood was negative. Fundus examination was normal with no evidence of any retinal hemorrhage or hypertension. In view of developmental delay with abnormal neurological examination, magnetic resonance imaging brain was done which revealed multifocal areas of altered signal intensity in periventricular deep white matter in bilateral frontal and parieto-occipital lobes, appearing hyperintense on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, and showing evidence of diffusion restriction, suggestive of areas of acute ischemia. Similar symmetrical hyperintense foci on T2 and FLAIR with diffusion restriction were also noted in bilateral caudate nuclei and putamina [Figure 1]. A well-defined, isointense to mildly hyperintense rounded lesion was seen in the left superior frontal lobe in the parasagittal region, with surrounding hypointense hemosiderin rim, suggestive of intraparenchymal hemorrhage. The findings of bilateral, multifocal areas of ischemia and hemorrhage in the brain were consistent with manifestations of CNS vasculitis.

Figure 1: Multifocal bilateral ischemic lesions involving white matter and gray matter nuclei in the brain. Hyperintense lesions are noted in bilateral frontal and parieto-occipital lobes involving the deep periventricular white matter on T2-weighted (red arrows – top row) and fluid-attenuated inversion recovery images (yellow arrows – middle row), showing evidence of diffusion restriction (blue arrows – bottom row). Similar T2 (single black arrows – top row) and fluid-attenuated inversion recovery (white arrows – middle row) hyperintense lesions are also noted in bilateral caudate nuclei and putamina, appearing hyperintense on diffusion-weighted images (double black arrows – bottom row)

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Investigations tailored to determine the underlying cause of vasculitis included antistreptolysin O titer <200 U/l, negative qualitative C-reactive protein, and the absence of antinuclear antibody, perinuclear antineutrophil cytoplasmic antibody (ANCA), and cytoplasmic ANCA. The skin biopsy revealed leukocytoclastic vasculitis around dermal vessels on hematoxylin and eosin staining [Figure 2]. Direct immunofluorescence study [Figure 3] revealed IgA and C3 deposits in the dermal vessel wall. The presence of nonthrombocytopenic and non-coagulative purpura, microscopic hematuria, and skin biopsy confirmed IgA vasculitis suggested the diagnosis of HSP. The European League against Rheumatism Collaborative Initiative criteria for HSP was also satisfied [Table 1].^[6] A close differential, acute hemorrhagic edema of infancy was excluded due to the absence of fever and edema in the lower limbs. The final diagnosis of the acute event was HSP with CNS vasculitis.

Figure 2: Skin biopsy with hematoxylin and eosin stain (magnification, ×10) showing leukocytoclasis around dermal capillaries

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Figure 3: Skin biopsy with direct immunofluorescence showing immunoglobulin A deposits (yellow arrows) around dermal capillaries

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Table 1: European League against Rheumatism Collaborative Initiative criteria for Henoch-Schonlein purpura

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The child was managed conservatively. The skin lesions and microscopic hematuria resolved by 7 days of hospitalization, and he was discharged. The patient was enrolled in the neurodevelopmental clinic for further management of the developmental delay, probably cerebral palsy. Physiotherapy and occupational therapy were initiated.

Discussion

HSP is largely a disease of childhood, with over 75% of patients exhibiting onset before the age of 10 years.^[1] The distribution of vasculitic involvement gives rise to the characteristic association of purpuric rash, arthralgia, abdominal pain, and nephritis. Rarely, vasculitis can extend to the cerebral blood vessels and cause edema, ischemia, infarction, and hemorrhage in the brain. Neurological manifestations of HSP were first described by Osler^[7] in 1914 as transitory hemiparesis and decreased level of consciousness. Since then, several case reports have described CNS manifestations, and a few studies have studied the prevalence and profile of CNS involvement.^[3],[5] In a review of 100 patients of HSP examined over a period of 20 years, Saulsbury described only two cases of seizures.^[3] Trapani et al. found a 3% incidence of headache without any other neurologic manifestations in 150 patients over 5 years.^[4] Pacheva et al. in their retrospective analysis identified only 1 patient with CNS involvement out of 112 patients with HSP.^[8] These studies clearly indicate that CNS involvement in HSP is very rare, estimated to be <1%. An important observation was that CNS involvement occurred mainly in patients with arterial hypertension or atypical presentation.^[3],[5],[8]

HSP is known to have relapses (within days to weeks of initial resolution of symptoms). Recurrences are reported in almost one-third of patients within a median duration of 9 months. In this case, the patient had developmental delay and presented with an acute illness that was diagnosed as HSP with CNS vasculitis. This led to two possible explanations. First, the child had developmental delay due to some unrelated cause and the acute event was the first episode of HSP. Second, the delay noted at 9 months could have been an unrecognized first episode of HSP (if the cutaneous manifestation was petechiae, they may have gone unnoticed) with CNS vasculitis that had no overt symptoms, but nonetheless damaged of the developing brain, and this acute event was a recurrent episode with overt cutaneous manifestations. An exhaustive literature search was unable to find any similar case report.

Most reports of cerebral vasculitis are based on imaging findings rather than histopathology. Occipital and posterior parietal lobes are predominantly involved, with brain edema and infarcts in these regions. Frontal, temporal, and cerebellar involvement is rare. This peculiar topography has led some authors to speculate that hemodynamic characteristics of the posterior circulation might favor preferential IgA deposition in these vessels.^[9]

HSP is usually a self-limited disease and management is primarily supportive in nature. There is no robust evidence for the use of corticosteroids in HSP with severe cerebral involvement, apart from a few case reports. Cyclophosphamide has also been employed in combination with steroids in a few cases. Whether these drugs have any additional benefits for CNS manifestations is unknown.^[10] Since our patient did not have any severe manifestations, we managed the child conservatively.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given consent for images and other clinical information to be reported in the journal. The guardian understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgment

Dr. Natasha Gupta (Specialist, Department of radio-diagnosis, GTB Hospital) provided guidance in writing radiology findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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