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Indian Pediatr 2019;56: 37-40 |
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Clinical Profile and Outcome of Pediatric
Sarcoidosis
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PKG Gunathilaka, Aparna Mukherjee, Kana Ram Jat,
Rakesh Lodha and SK Kabra
From Department of Pediatrics, All India Institute
of Medical Sciences, New Delhi, India.
Correspondence to: Prof SK Kabra, Department of
Pediatrics, All India Institute of Medical Sciences,
New Delhi 110 029, India.
Email: [email protected]
Received: June 15, 2018;
Initial review: August 13, 2018;
Accepted: October 27, 2018.
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Objectives: To document clinical
features and outcome of children with sarcoidosis. Methods: Case
records of 18 children (mean (SD) age 9 (2.2) years) diagnosed
with sarcoidosis between 2006 and 2016 were reviewed. All children were
followed up every 2-3 months and monitored for clinical and laboratory
parameters. Their treatment and outcome were recorded. Results:
Clinical features at the time of diagnosis were fever (83%), uveitis
(50%), difficulty in breathing (44%), hepatosplenomegaly, weight loss,
arthritis and peripheral adenopathy. Imaging findings included: hilar
adenopathy (94%), abdominal nodes (50%) and pulmonary infiltrates (44%).
All children were treated with steroids (range 6-12 months) and weekly
low dose oral methotrexate. All patients showed significant improvement
over a mean (SD) duration of follow-up of 3.1 (0.9) years, as assessed
by resolution of clinical symptoms, and improvement in spirometry
parameters, erythrocyte sedimentation rate, and serum angiotensin
converting enzyme levels. Conclusions: Children with
sarcoidosis seem to respond well to systemic steroids and low dose
methotrexate. Delayed diagnosis and ocular involvement are probably
associated with poor outcome.
Keywords: Corticosteroids,
Hilar lymphadenopathy, Non-caseating granuloma.
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P ediatric sarcoidosis is a chronic disease
characterized by non-caseating granulomatous inflammation [1]. It most
commonly affects young adults, and is very rare in children [2].
Sarcoidosis is a multisystem disorder; however, mediastinal
lymphadenopathy, pulmonary parenchymal infiltration, and cutaneous and
ophthalmic disease are common. Moreover, it may involve liver, central
nervous system and kidneys [3]. In young children (<5 year old), a triad
of skin rash, uveitis and arthritis is more common than pulmonary and
mediastinal involvement [4]. Information on course of illness, effective
treatment and outcome on childhood sarcoidosis is limited to few
reports. Diagnostic criteria are well defined but monitoring and
treatment regimen are not well defined. We describe our experience of
sarcoidosis in children with emphasis on role of treatment regimen that
included methotrexate.
Methods
We reviewed the case records of children with
diagnosis of sarcoidosis between 2006 and 2016, who were followed-up at
Pediatric Pulmonology services at AIIMS, New Delhi, India. Details
including clinical symptoms and signs, investigations, treatment given,
follow-up and outcomes were recorded in a predesigned proforma. The
study was approved by Institute Ethics Committee.
Diagnosis of sarcoidosis was based on clinical
features, documentation of non-caseating granuloma from various body
tissues, raised serum Angiotensin converting enzyme (ACE) levels and
raised urinary calcium to creatinine ratio. Patients who had doubtful
diagnosis or who were confirmed with an alternative diagnosis, were
excluded from the study.
Treatment protocol consisted of systemic steroids,
low-dose weekly methotrexate or other medications as indicated. All
children were followed-up every 2-3 months. On each visit, children were
evaluated clinically, spirometry was done in older children, and
hematological investigations and liver and kidney function tests were
performed. Other laboratory investigations and imaging were carried out
as indicated.
Data were processed with Microsoft Excel, and
analyzed with SPSS V 16.0. Statistical significance was analyzed with
paired t test and Wilcoxon signed rank test.
Results
A total of 18 children (10 boys) diagnosed with
sarcoidosis during study period were included. The mean (SD) age at
diagnosis and onset of disease was 9 (2.5) and 7.5 (2.0) years,
respectively. All patients were symptomatic at presentation. Clinical
symptoms, signs and laboratory findings are described in Table
I.
TABLE I Clinical Features at Presentation in Children with Sarcoidosis (N=18)
Clinical features |
Number (%) |
Fever |
15 (83) |
Difficulty in respiration |
8 (44) |
Uveitis |
9 (50) |
Hepatomegaly |
8 (44) |
Splenomegaly |
7 (38) |
Enlarged peripheral nodes |
6 (33) |
Weight loss |
6 (33) |
Arthritis of large joints |
5 (28) |
Skin rash |
5 (28) |
Impaired vision |
3 (17) |
Cough |
2 (11) |
Erythema nodosum |
1(6) |
Seizure |
1 (6) |
Eight children had previously received
anti-tubercular therapy. Six children had Mantoux test positivity; four
of them had already received anti-tubercular therapy and remaining two
were administered prophylactic isoniazid therapy after ruling out active
tuberculosis while they were prescribed systemic steroid therapy.
Sixteen (88%) children had intrathoracic involvement
with hilar lymphadenopathy; eight of them had parenchymal involvement
classifying them as stage 2 illness. None had stage 3 or 4 illness. Nine
(50%) children had abdominal lymphadenopathy.
A tissue diagnosis was available in 16 (88%)
children, and all showed non-caseating granulomatous inflammation with
negative stain for acid fast bacilli. The sites of biopsy included lymph
node in 10 (63%), skin in 4 (25%), lacrimal gland in 1 (6%) and liver in
1 (6%).
Table II shows laboratory parameters from
diagnosis to remission. Laboratory markers [mean (SD)] documented at
diagnosis were: serum calcium 10.6 (0.96) mg/dL, serum phosphate 4.16
(0.68) mg/dL, serum alkaline phosphatase 259 (120) mg/dL, serum
25-hydroxy vitamin D 150.2 (20.9) ng/mL, and urinary calcium: creatinine
ratio 0.54 (0.21). None of the patients had rheumatoid factor,
anti-nuclear antibody or anti-nuclear cytoplasmic antibody test
positive. Eight children had pulmonary function assessments at diagnosis
and at follow-up. The FVC (Forced Vital Capacity), FEV1 (Forced
Expiratory Volume in 1 sec), and PEF (Peak Expiratory Flow)
significantly improved at remission (Table II). Therapy
with systemic steroids (oral prednisolone) was commenced (dose 1-2
mg/kg/day) for 17 patients while one patient experienced a spontaneous
recovery. Steroids were tapered successfully over mean (SD) duration of
7.6 (1.9) months (range 6-12); the mean (SD) duration to achieve
remission was 2.5 (0.6) months. However, two patients experienced
relapses while tapering off steroids; they subsequently had successful
outcome.
TABLE II Comparison of Laboratory Parameters at Diagnosis and at Remission
Parameters |
At Diagnosis |
At Remission |
P value |
Blood parameters (n=18) |
Total leucocyte count (per mm3) |
10861 (3202) |
6346 (847) |
<0.001 |
Hemoglobin (g/dL) |
9.5 (0.8) |
11.6 (0.7) |
<0.001 |
Erythrocyte sedimentation rate |
51 (19.7) |
17 (4.7) |
0.001 |
Serum angiotensin converting enzyme (U/mL) |
147 (48.0) |
62 (11.4) |
0.001 |
Pulmonary function test parameters (n=8) |
Forced vital capacity (% of predicted) |
62.5 (17.3) |
90.5 (3.0) |
0.01 |
FEV1 (% of predicted) |
63.5 (17.0) |
88.5 (2.5) |
0.02 |
FEV1/FVC (% of predicted) |
88.1 (3.8) |
90.6 (2.8) |
0.41 |
Peak expiratory flow (% of predicted) |
70.1 (10.5) |
90.1 (2.0) |
0.02 |
All values are in mean (SD); FEV1: Forced
Expiratory Volume in 1 s. |
Weekly oral methotrexate 10 mg/m 2/week
was administered in 11 (61%) patients and continued for 9-12 months with
significant improvement. Oral hydroxychloroquine 5 mg/kg/day for 12
months were prescribed to 4 patients, and azathioprine to 2 patients
along with steroids.
Seventeen patients followed-up regularly. Mean (SD)
duration of follow-up was 3.12 (0.88) years with overall outcome of
complete recovery in all. Three children who had uveitis and cataract
needed surgical intervention; however, two continued to be visually
impaired even after surgical therapy.
All children who received systemic steroids developed
transient adverse effects (weight gain, cushingoid appearance); however,
none of them had steroid-induced impaired glucose tolerance,
hyper-tension or cataract. No significant adverse effects were
documented for methotrexate, hydroxychloroquine and azathioprine.
Sixteen children had school absenteeism of minimum of
6 months during the course of illness; four children could never be
readmitted to school after diagnosis.
Discussion
In this series, we described clinical manifestations,
course of illness and treatment outcomes in 18 children with sarcoidosis.
All had multisystem involvement with intrathoracic findings in majority.
Systemic steroids and methotrexate improved their outcome.
Prevalence of sarcoidosis in literature has bimodal
distribution with a small peak around 14 years [5,6]. Actual prevalence
and incidence of sarcoidosis among pediatric population is unknown
largely due to its rarity. One of the largest series on pediatric
sarcoidosis was a Danish study where 48 cases (35 confirmed by
histology) were reported [2]. The estimated incidence is approximately
0.25 per 100,000 per year under 15 years according to Danish study [2].
Sarcoidosis has multisystem involvement in majority
of patients [2,6-8]. Ophthalmological manifestations, principally
uveitis and conjunctival granuloma are the commonest manifestations in
younger age group [9,10]. In our study, half the group (9/18 children)
had ocular involvement as uveitis and conjunctival involvement and three
children had blindness and underwent surgical management. Pulmonary
involvement in children is reported in around 40% [2,7,11]. Skin
manifestation in childhood sarcoidosis occurs in up to one fourth of
cases in the form of papules and plaques [12].
Demonstration of non-necrotizing epithelioid
granuloma without any evidence of tuberculosis is the hallmark for
diagnosis of sarcoidosis [13]. The index series had non-necrotizing
epithelioid granuloma in biopsy in almost all cases. Erythrocyte
sedimentation rate (ESR) and angiotensin converting enzyme (ACE) may be
markers of disease activity [6,14]. We also found significantly decrease
in ESR and ACE levels with treatment.
Systemic steroids (oral prednisolone) and
methotrexate are cornerstone of the therapy of sarcoidosis [6]. In this
series also, children responded well to prednisolone and methotrexate.
There are some limitations of our study. As it was a
retrospective case record review, some data were missing and comparison
of different therapeutic measures was difficult. The small sample size
due to rarity of this condition in children was a major limitation.
To conclude, pediatric sarcoidosis is a rare
multi-system disease with significant proportion having intrathoracic
involvement. Tissue examination is essential part of diagnosis. Serum
ACE level and ESR are helpful in monitoring disease activity. It has
good prognosis in pulmonary involvement if diagnosed in early stage.
Late diagnosis may have poor prognosis with regard to ocular and lung
disease.
Contributors: PKGG ad SKK: study
conceptualization, data collection, analysis and manuscript writing; AM:
data analysis and manuscript writing; KRJ: manuscript writing; RL: study
conceptualization, data analysis and manuscript writing; RL, KRJ, SKK:
revised the manuscript critically for important intellectual content.
All authors approved final version of manuscript.
Funding: None; Competing Interest: None
stated.
What this Study Adds?
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High index of suspicion is required to diagnose sarcoidosis
in children as many cases are treated as tuberculosis.
·
Sarcoidosis in children
responds well to steroids and methotrexate, if treatment is
started early.
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