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 Table of Contents  
Year : 2021  |  Volume : 16  |  Issue : 2  |  Page : 127-132

Profile of pediatric vasculitides – Prospective hospital-based data from eastern India

1 Department of Pediatric Medicine, Pediatric Rheumatology Clinic, IPGMER and SSKM Hospital, Kolkata, West Bengal, India
2 Department of Community Medicine, Medical College, Kolkata, West Bengal, India

Date of Submission09-Dec-2019
Date of Acceptance15-Apr-2020
Date of Web Publication25-Jun-2021

Correspondence Address:
Dr. Tanushree Mondal
Department of Community Medicine, Medical College, Kolkata, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_180_19

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Background: The pediatric vasculitides are multisystem autoimmune disorders involving the blood vessels of varying sizes. Wide geographic and ethnic variations are noted in terms of incidence and clinical features.
Materials and Methods: This prospective, observational study was carried out over a period of 4 years from 2015 February to 2019 February in a tertiary care referral hospital to delineate the epidemiological pattern, clinical features, and pathological characteristics of pediatric vasculitides. All consecutive patients with vasculitis defined by the American College of Rheumatology and Chappel Hill Consensus Criteria diagnostic criteria were included in the study. They underwent relevant investigations and were treated as per the standard guidelines.
Results: Of the total 110 patients with different types of vasculitis, 90% (n = 99) had primary vasculitis and the rest had secondary (10%, n = 11). Immunoglobulin A vasculitis (Henoch–Schonlein Purpura) (HSP) (n = 53, 48.19%) and Kawasaki disease (KD) (n = 35, 31.82%) were the most frequent types of the vasculitis followed by Takayasu arteritis and polyarteritis nodosa. Secondary vasculitides included those associated with systemic lupus erythematosus, juvenile idiopathic arthritis, scrub typhus infection, and drug penicillamine. Various typical and atypical features along with a definite seasonal pattern of their prevalence had been documented.
Conclusion: A profile of pediatric vasculitides with a specific trend in their prevalence and seasonal pattern has been documented. HSP and KD constitute the predominant types of pediatric vasculitides. KD, although diagnosed more often than previous, HSP still outnumbers KD in Eastern India.

Keywords: Pediatric, profile, vasculitis

How to cite this article:
Saha A, Sarkar S, Mondal T. Profile of pediatric vasculitides – Prospective hospital-based data from eastern India. Indian J Rheumatol 2021;16:127-32

How to cite this URL:
Saha A, Sarkar S, Mondal T. Profile of pediatric vasculitides – Prospective hospital-based data from eastern India. Indian J Rheumatol [serial online] 2021 [cited 2021 Sep 23];16:127-32. Available from:

  Introduction Top

Pediatric vasculitides are multisystem autoimmune disorders involving different sizes of blood vessels. These may be either primary or secondary to another illness, autoimmune disease, drugs, or malignancy.[1] They range in severity from a self-limited single-organ disorder to a life-threatening disease with the consequence of multi-organ failure. The objective of the study was to delineate the epidemiological pattern, etiology, clinical features, and pathological characteristics of different types of pediatric vasculitides in a tertiary care referral hospital in the Eastern part of India. An overview of the data is presented here.

  Materials and Methods Top

It was an institution-based, prospective, observational study carried out over a period of 4 years from 2015 February to 2019 February. Clearance from the institutional ethics committee was obtained. Written informed consent was obtained from the parents of all the participants <7 years and assent from those >7 years. All the consecutive patients between the ages of 1 and 12 years presenting with vasculitis were included in the study. The age limit of 12 years was selected since the children up to that age are being treated in the pediatric department as per the institutional policy. This study was conducted by an integrated approach with the support from the department of dermatology and pathology.

Detailed history, physical examination, and laboratory parameters were documented in a predesigned pro forma. All clinical data were recorded during the acute presentation and follow-up. The American College of Rheumatology (1990) and Chappel Hill Consensus Criteria (2012) that updated the 1994 consensus recommendations were used for the diagnosis of vasculitides in the present study.[2],[3],[4] Digital photographs of the lesion were taken. Routine and specific laboratory investigations were sent as relevant. The baseline investigations included complete blood count, erythrocyte sedimentation rate (ESR), routine urine and stool examination, liver function test, serum urea, serum creatinine, and chest X-ray. The specific investigations included hepatitis B surface antigen and anti-hepatitis C virus; Integrated Counseling and Testing Centre for testing HIV; mantoux (5TU); antistreptolysin O (ASO) (nephelometry); blood culture (Bactec); antinuclear antibody (Hep20-10, IIFT); antineutrophil cytoplasmic antibody (ANCA) (granulocyte, IIFT); C-reactive protein (CRP) (nephelometry); serum immunoglobulin (Ig) G, IgA, and IgM (nephelometry); and complement level (nephelometry). Other tests included echocardiography, electrocardiography, electromyography, nerve conduction velocity, computed tomography (CT), magnetic resonance imaging, magnetic resonance angiography, and CT angiography. These specialized tests were done wherever applicable. For the histopathological examination, a punch biopsy was taken from the cutaneous lesions, in a solution of 10% buffered formaldehyde. Another punch biopsy was taken for direct immunofluorescence (wherever appropriate) in a suitable transport medium like Michel's transport medium.

Data were analyzed by statistical tests using Statistica version 6. (Tulsa, Oklahoma: StatSoft Inc. 2001) and presented as mean for numerical variables and percentages for categorical variables.

  Results Top

A total of 110 patients diagnosed as having vasculitis were included in the study. Among them, 64 were male and 46 were female (M: F ratio of 1.4:1). The mean age of presentation was 6.88 ± 2.45 years. Primary vasculitis (n = 99, 90%) was more common than the secondary vasculitis (n = 11, 10%).

The relative frequency of primary vasculitis was IgA vasculitis (Henoch–Schonlein purpura) (HSP) (n = 53, 48.19%), Kawasaki disease (KD) (n = 35, 31.82%), Takayasu arteritis (n = 3, 2.72%), and polyarteritis nodosa (PAN) (n = 5, 4.54%). Secondary vasculitis constituted systemic lupus erythematosus (SLE) (n = 5, 4.54%), systemic juvenile idiopathic arthritis (sJIA) (n = 2, 1.81%), urticarial vasculitis (n = 2, 1.81%), anti-thymocyte globulin-induced Arthus reaction (n = 1, 0.9%), penicillamine-induced ANCA-positive vasculitis (n = 1, 0.9%), infection (scrub typhus)-induced vasculitis (n = 2, 1.81%) [Table 1], and HSP and KD (n = 88, 80%), altogether are the majority of the vasculitis in the present series [Figure 1]. All other cases constitute only one-fifth of the cohort indicative of the rarity of the other types of vasculitis.
Table 1: Relative frequency of different types of vasculitis (based on the American College of Rheumatology and Chappel Hill Consensus Criteria classification)

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Figure 1: Diagrammatic representati,non of different types of pediatric vasculitis

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The most frequent primary vasculitis was HSP (n = 53, 48.19%). The mean age of the presentation was 7.5 years (range: 5–12 years) with a female preponderance (M:F =1:1.45). All of them had palpable purpura (n = 53,100%). Gastrointestinal (GI) involvements were noted in 44 patients (n = 44, 83%). Four patients had orchitis and two had convulsions. Two patients had acute nephritis as a part of their multisystem presentation. One child presented with recurrence after 3 months of the initial episode. Urinalysis showed microscopic hematuria (n = 10) and proteinuria (2 + or less) (n = 9). Among the uncommon features notable were raised ASO titer (n = 10), low C3 without any renal involvement (n = 4), and raised serum IGA (n = 8). Histopathological examination of dermal lesions (done in 45 patients) revealed predominantly perivascular infiltrate of lymphocytes in most of the specimens (n = 40, 88.9%). Direct immunofluorescence (DIF) was done in 28 patients. Among them, 20 were DIF positive and 8 were DIF negative. All patients with positive DIF showed 100% positivity for IgA, C3, and fibrin deposition. IgM was positive in two patients. Treatment of HSP was symptomatic and supportive with the maintenance of good hydration, nutrition, and electrolyte balance. Medications include analgesic ibuprofen to control the joint pain (n = 38), antihistaminic hydroxyzine (n = 48), and oral prednisolone (n = 10). Five patients required antihypertensive. Two cases with a multisystem presentation with severe symptoms required intravenous (IV) methylprednisolone. All the patients achieved remission with standard treatment. The mean duration of the disease was 14.7 days. They were followed up at the pediatric rheumatology clinic with serial monitoring of blood pressure, urinalysis, and serum creatinine. Those with microscopic urinary abnormalities recovered within the next few weeks. Those with severe symptoms developed persistent proteinuria and chronic kidney disease (CKD) requiring dialysis (n = 2) in a month.

KD was the second most common vasculitis (31.82%, n = 35). The mean age of presentation was 5.3 years. Males outnumbered females (M:F = 4:3). The majority had a typical presentation. Incomplete KD was diagnosed in nine patients. Atypical features include perianal desquamation (n = 9, 25.7%), diarrhea (n = 7, 20%), and arthritis (n = 4, 11.4%). Four patients developed secondary hemophagocytic lymphohistiocytosis (HLH) (n = 4, 11.4%). One of them was associated with dengue. One patient, who had been diagnosed as incomplete KD 2 years back, presented with recurrence of KD symptoms. The coronary artery involvement was documented in 7 patients (20%) on echocardiography. The involvement was mostly in the left main coronary artery (n = 4), followed by the left anterior descending artery (n = 1), circumflex coronary artery (n = 1), and the right main coronary artery (n = 1). All KD patients received IV immunoglobulin (IVIG) at a dose of 2 g/kg over 8–12 h. IVIG resistance was noted in three patients who responded later with repeat doses of IVIG. Aspirin was started in all patients at 80–100 mg/kg/day, in four divided doses, followed by at 5 mg/kg once a day when fever got subsided. All of them underwent monitoring with ESR and CRP till the normalization of these activity markers. Follow-up echocardiography with Doppler was done in all patients.

All the three patients with Takayasu disease were female with a mean age of presentation 7.7 years. All of them had systemic hypertension and involvement of the descending thoracic aorta. They received prednisolone, antiplatelet, and antihypertensive, while methotrexate was given to one patient.

In the present series, five patients had PAN (M:F ratio: 3:2, mean age of onset: 5.5 years). One of them had cutaneous PAN. All had fever, myalgia, and skin involvement. One patient with a history of consanguinity and ischemic stroke was suspected to have a deficiency of adenosine deaminase-2. However, further investigation could not be possible due to financial constraints. SLE-associated vasculitis was found in 5 cases (4.54%). One of them had central nervous system vasculitis. All received treatment with prednisolone, antihypertensive, and azathioprine. Two patients received rituximab. They showed clinical improvement on follow-up with normalization of activity markers. We had two patients with necrotizing vasculitis and one of them had pan digital gangrene in the hands. They were treated with doxycycline and surgical intervention.

A seasonal pattern of vasculitis has been observed in our study [Figure 2]. The comparison of HSP and KD, the major vasculitides, has been presented here. The incidence of HSP was common in autumn (October–November) and that of KD in the winter months (December–February). The prevalence of overall cases was less during the monsoon.
Figure 2: Seasonal trend of two major vasculitides (Henoch–Schonlein purpura and Kawasaki disease)

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  Discussion Top

The present study documented HSP (n = 53, 48.19%) as the most common vasculitis, followed by KD (n = 35, 31.82%). This pattern is similar to the Western and Indian data.[5],[6],[7],[8] The majority of the studies in pediatric vasculitides are available from western countries, while only a few from India.[6],[7],[8]

In our previously published data of 7 years (2004–2011), out of 158 cases, HSP was the major vasculitis (n = 90, 56.9%) followed by KD (n = 38, 24%).[5] The present study documented a similar trend, as HSP (n = 53, 48.19%) outnumbered KD (n = 35, 31.82%), but the percentage of KD cases was greater compared to the earlier report (31.8% vs. 24%). In addition, a few rare etiologies of pediatric vasculitis have been recorded, i.e. antiglomerular basement membrane (GBM) vasculitis, scrub typhus vasculitis, penicillamine induced vasculitis. No case of Wegener's granulomatosis has been diagnosed in the present series. A comparative data in relative frequency, now and then, had been shown [Table 2].
Table 2: Relative frequency of different types of vasculitis: comparative data

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In one large series, published from the United States, of 434 vasculitis cases, 213 (49.1%) were HSP and 97 (22.4%) were KD.[6] Ozen et al. in their series of 376 patients, published from Turkey, showed a similar pattern with HSP more frequent than KD (218 vs. 78).[8] On the contrary, KD was more frequent than HSP in the Canadian series.[7] The diagnosis of KD in India has increased over the past decades. One hospital-based data from Chandigarh showed that the KD, and not HSP, was the most common pediatric vasculitis at that center.[9] However, in our study, HSP had outnumbered the KD.

Among the patients of HSP, the mean age at presentation was 7.5 years, which is comparable to that reported earlier.[10] Skin involvement was found in all patients that included purpuric rash (100%) and subcutaneous edema (48.1%). Abdominal pain preceded the rash in 6 (22.2%) patients. Arthritis, angioedema, was an initial presentation in two patients. Several other clinical features are comparable to the study cohort reported earlier.[11],[12],[13] Neurological manifestations are unusual in HSP which include coma, subarachnoid hemorrhage, seizures, and Guillain–Barre Syndrome.[10] One child had an initial presentation of fever with convulsions and later developed the typical rash of HSP. Another one had convulsion on day 3 of illness. Renal involvement is less frequent in our series. Only two patients had acute nephritis. The outcome of the patients in our series was satisfactory with standard supportive treatment. Severe cases of arthritis required corticosteroids at a dose similar to that proposed for severe skin or GI disease as reported in other series.[14] Rare patients with severe skin disorders may need dapsone or azathioprine. Additional immunosuppressive agents such as methotrexate and hydroxychloroquine may have a role in arthritis.[15] Two patients in our study developed CKD and became dialysis dependent.

KD is classically described as a disease of younger children (<5 years). However, our study had shown a greater number of older children (>5 years) (n = 25) with a higher mean age of 5.3 years. Male preponderance was similar to various other parts of India.[16],[17] In our study, majority had classic KD (n = 26, 74.3%), while only nine patients were diagnosed as incomplete KD (n = 9, 25.7%). Fever, rash, nonexudative conjunctivitis, and periungual desquamation were found in all patients. Coronary artery involvement was detected in seven patients. The incidence is similar to Chandigarh data.[17] Four patients with KD developed secondary HLH and one of them had associated dengue. The case of dengue and KD with HLH has been reported by us.[18] Recurrent KD in India has rarely been reported.[19] One patient of our study cohort, who was diagnosed earlier as incomplete KD, had recurrence after 2 years. The case has been published as the first case of recurrent Kawasaki from Eastern India.[20] IVIG is the preferred and most effective treatment when given within 10 days of fever. A higher dose of aspirin is used in our study, although most clinicians prefer the low dose at 30–50 mg/kg/day during the acute phase of KD.[21] In case of refractory KD, administration of infliximab is effective with prompt reduction of fever as shown in a North Indian study.[22] In the present study, none of our patient received infliximab. Although three cases were IVIG refractory, they responded well to repeat doses of IVIG. Dexamethasone was given to those who developed HLH.

All the three patients with Takayasu disease in our study cohort were female. The mean age of presentation was 7.7 years, which is earlier compared to other Indian studies.[23] All had hypertension at the initial clinical presentation. Echocardiography revealed left ventricular dysfunction in two patients. All had descending thoracic aorta involvement in angiography. These findings are comparable to earlier Indian studies.[23]

Five of our patients had PAN (M: F ratio 2:1, mean age of onset 5.5 years), of which one had cutaneous PAN. All had fever, myalgia, and skin involvement. The diagnosis was established in all patients by skin biopsy which showed necrotizing vasculitis of the medium-sized vessels. None had renal or pulmonary involvement. Our findings are comparable to our previous literature from Eastern India.[24]

Among the small-vessel group, two patients were diagnosed as hypocomplementemic urticarial vasculitis based on the histopathological finding. One patient with renal failure was confirmed as anti-GBM disease.

Vasculitides secondary to systemic disease and drugs are not uncommon.[25] In the present study, seven cases had been diagnosed as “vasculitis associated with systemic disease.”

Of these seven cases, five were associated with SLE, while two others with sJIA. Four cases were classified in the group “vasculitis associated with probable etiology.” Drug-associated vasculitides were noted in two children. One of them had aplastic anemia and developed an Arthus reaction (type III hypersensitivity reaction) following the administration of anti-thymocyte globulin. The other patient with Wilson's disease developed ANCA-positive vasculitis secondary to penicillamine. Penicillamine causing such vasculitides has rarely been reported.[26]

Over the past 3 years, the incidence of scrub typhus has increased in Eastern India. Two patients with scrub typhus had developed vasculitis and one of them had pan digital gangrene in the hand. Focal or disseminated necrotizing vasculitis caused by the endothelial cell destruction and the perivascular leukocytic infiltrations are the main pathological changes in those cases.[27]

The major vasculitides in our study exhibited a specific seasonal trend. HSP cases were found mostly during October–November, while KD cases in the winter season, around December to February. Seasonal predilection was also documented in the study from the Northern part of India where both the vasculitis occurring around October–November.[9]

The discovery of novel biomarkers in recent times has revolutionized the methods of diagnosis, monitoring, predicting treatment response, and prognosis in pediatric vasculitis. The use of modern “omics” technologies has shown the most promising advances.[28] Some of the newer biomarkers, namely factor XIII in HSP, NT-proBNP in KD, PTX3 in Takayasu arteritis, von Willebrand factor antigen in PAN, eotaxin-3 in Churg–Straus vasculitis, and urinary soluble CD163 for renal vasculitis in ANCA-associated vasculitides are potentially relevant.[29] The future of the vasculitis research will be focusing on these new biomarkers; however, it is difficult to carry out such studies in a resource-constrainted setup.

  Conclusion Top

The pediatric vasculitides are not uncommon in this part of the world. A specific trend has been documented in the present hospital-based profile. HSP and KD constitute the predominant types of vasculitides and HSP outnumbered KD in the present series. They have shown a specific seasonal trend in their occurrence. However, long-term multicenter studies involving a large number of patients and recent biomarkers are needed for proper delineation of the entire spectrum.

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  References Top

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Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92.  Back to cited text no. 4
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  [Table 1], [Table 2]


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