Paediatric rheumatology Clinical profile, long-term follow-up and outcome of juvenile systemic scleroderma: 25 years of clinical experience from ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Paediatric rheumatology
Clinical profile, long-term follow-up and
outcome of juvenile systemic scleroderma:
25 years of clinical experience from North-West India
A.K. Jindal1, P. Patra1, S. Guleria1, A. Gupta1, S. Bhattad1, A. Rawat1,
D. Suri1, V. Pandiarajan1, A. Bishnoi2, S. Dogra2, S. Singh1
1
Allergy Immunology Unit, Department ABSTRACT Conclusion. We describe the largest
of Paediatrics, Postgraduate Institute Objective. To describe the clinical pro- single-centre cohort with longest fol-
of Medical Education and Research, file, long-term follow-up and outcome low-up of juvenile systemic scleroder-
Chandigarh;
of juvenile systemic scleroderma (JSSc) ma from India.
2
Department of Dermatology,
Venereology and Leprology, Postgraduate from a tertiary care referral hospital in
Institute of Medical Education and North-West India. Introduction
Research, Chandigarh, India. Methods. A review of case records Juvenile systemic scleroderma (JSSc)
Ankur Kumar Jindal, MD, DM was performed and children with JSSc is a multisystem connective tissue dis-
Pratap Patra, MD (disease onset
Juvenile systemic scleroderma / A.K. Jindal et al.
while diffuse SSc was labelled when Table I. Clinical and laboratory manifestations in the study cohort.
skin thickening involved upper arms,
Clinical manifestation % (n=40)
thighs, anterior chest, or abdomen. Pa-
tients having overlap syndromes were Skin involvement
also included in the analysis. Raynaud’s phenomenon 40/40 (100%)
Modified Rodnan Skin Score (mRSS) Skin tightness 40/40 (100%)
Calcinosis 10/40 (25%)
was used to quantify severity of skin Telangiectasia 7/40 (17.5%)
tightness (17) and juvenile systemic Acro-osteolysis 4/40 (10%)
scleroderma severity score (J4S) (18) Digital gangrene 3/40 (7.5%)
Cutaneous ulcers (Fig. 1A) 14/40 (35%)
was used to assess severity of systemic
Lung involvement 16/40 (40%)
disease. However, mRSS and J4S have Dyspnea on exertion 4/40 (10%)
only been administered during last 4 Abnormal pulmonary function test (Moderate to severe restriction) 10/32 (31.2%)
years and could not be assessed regu- Abnormal CT chest 13/26 (50%)
Reduced DLCO 1 patient
larly in all patients. PAH 5/40 (12.5%)
Pulmonary function tests (PFT) includ- Gastrointestinal involvement 8/40 (20%)
ed forced expiratory volume 1 (FEV1) Dysphagia 5/40 (12.5%)
and forced vital capacity (FVC). Re- Dilated oesophagus on CT 2 patients
Abnormal barium swallow 2 patients
strictive pattern was classified as mild Abnormal oesophageal manometry 2 patients
when FVC was between 70-80%; mod-
Cardiac involvement
erate, when FVC was between 60-70%; Tricuspid regurgitation 3/40 (7.5%)
moderately severe, when FVC was be-
tween 50–60% and severe, when FVC Musculoskeletal involvement
Arthritis 10/40 (25%)
was less than 50%. High-resolution Contractures leading to restriction of joint movements 16/40 (40%)
computed tomography (HRCT) was Positive antinuclear antibody (ANA) 34/39 (87.1%)
carried out to assess pulmonary in- Speckled 15/39 (38.4%)
Nucleolar 8/39 (20.5%)
volvement in selected patients. HRCT
Diffuse 2/39 (5.1%)
chest was also repeated in some patients Mixed speckled and nucleolar 3/39 (7.6%)
depending on clinical assessment. Indi- Mixed diffuse and nucleolar 4/39 (10.2%)
cations included development of dysp- Cytoplasmic 1/39 (2.5%)
Cytoplasmic and nucleolar 1/39 (2.5%)
nea on exertion, cough, crepitations on Antibodies against extractable nuclear antigen 15/18 (83.3%)
chest auscultation, clubbing or restric- Anti U1RNP 5 patients
tive pattern on FVC. Routine follow-up Anti Scl-70 3 patients
CT was not performed in all patients. Anti SSA/Ro52 2 patients
Anti PMScl 2 patients
Echocardiography and 12-lead electro- Anti Jo1 2 patients
cardiography (ECG) were used to as- Anti Sm 2 patients
sess cardiac involvement. Pulmonary Anti RiboP 1 patient
artery hypertension (PAH) was defined Anti PCNA 1 patient
Overlap syndrome 22/40 (55%)
as mean pulmonary arterial pressure SLE 8/22 (36.3%)
(mPAP) ≥ 25 mmHg. JDM1/22 (4.5%) 17/22 (77.2%)
Initially, patients were being referred to PM 1/22 (4.5%)
the Department of Dermatology in our JIA 6/22 (27.2%)
Lost to follow-up 6/40 (15%)
institute for dermatoscopic evaluation Mortality 6/40 (15%)
of nail fold capillary changes. We have
now been performing nail fold capil- CT: computed tomography; DLCO: diffusion capacity of lung for carbon monoxide; JDM/PM: juve-
nile dermatomyositis/polymyositis; JIA: juvenile idiopathic arthritis; PAH: pulmonary artery hyperten-
laroscopy (Optilia Digital Capillaros-
sion; PCNA: proliferating cell nuclear antigen; RNP: ribonucleoprotein; Ribo P: ribosomal P; SLE:
copy System) ourselves since June 2018. systemic lupus erythematosus.
However, nailfold capillaroscopy or *3 patients had only cutaneous signs of JDM and no clinical weakness or elevated muscle enzymes.
dermatoscopy could not be performed in
all patients and this assessment was not [ANA] (using indirect immunofluores- day) as maintenance therapy for a vari-
carried out routinely during follow-up. cence method with 1:40 dilution and able period of 2–5 years. Patients with-
Patients with gastrointestinal symptoms immunoblot to assess for antibodies out any major organ disease were ini-
(dysphagia or reflux) were evaluated against extractable nuclear antigen). tiated on methotrexate (15–20 mg/m2/
using either barium swallow studies Patients who had evidence of interstitial week subcutaneous). Corticosteroids
or oesophageal manometry. Labora- lung disease (ILD) were treated with in- (oral prednisolone/intravenous methyl-
tory investigations included: complete jection cyclophosphamide pulses (500– prednisolone or intravenous dexameth-
blood count, renal function tests, urine 750 mg/m2/pulse) for 6–12 months fol- asone) were also used in patients with
examination and antinuclear antibody lowed by azathioprine (2–2.5 mg/kg/ glomerulonephritis, ILD, arthritis or
S-150 Clinical and Experimental Rheumatology 2021Juvenile systemic scleroderma / A.K. Jindal et al.
Fig. 1. Showing changes of peripheral vascular disease in patients with JSSc.
A. Digital tip ulcers in an 8-year-old boy with JSSc;
B. Nailfold capillaroscopy in a 12-year-old girl with JSSc showing active scleroderma pattern (giant capillaries, avascular areas and haemorrhages).
myositis. Raynaud phenomenon (RP) Table II. Treatment details of all patients.
was managed using calcium channel
Treatment % (n=40)
blockers (nifedipine). Patients with rap-
idly progressing digital gangrene were Oral prednisolone 22/40 (55%)
also managed using endothelin receptor Intravenous methylprednisolone pulse 4/40 (10%)
antagonists (bosentan) and prostaglan- Intravenous dexamethasone 2/40 (5%)
Methotrexate 23/40 (57.5%)
din E1 (alprostadil). Eight patients who
Cyclophosphamide pulses 11/40 (27.5%)
were not coming for regular follow-up Azathioprine 10/40 (25%)
were contacted through telephone and/ Mycophenolate mofetil 3/40 (7.5%)
or letters. Two amongst these reported Rituximab* 1/40 (2.5%)
to the clinic while the remaining 6 were Plasma exchange* 1/40 (2.5%)
Hydroxychloroquine 13/40 (32.5%)
lost to follow-up.
Bosentan 2/40 (5%)
Alprostadil 1/40 ( 2.5%)
Results
Forty patients (28 girls and 12 boys; *Indication: diffuse alveolar haemorrhage
F:M ratio= 2.3:1) were diagnosed with
SSc (including 22 children with over- Skin biopsy was performed in 15 pa- malities on CT chest had moderate to
lap) in last 25 years. Mean age at symp- tients. It showed changes suggestive of severe restriction on PFT (7/13, 53.8%),
tom onset was 7.75±3.19 years, while scleroderma (thickened basement mem- 4 had mild restriction and 2 had normal
mean age at diagnosis was 10.02±2.48 brane, lymphomononuclear infiltration PFT. Moderate to severe restriction on
years with a mean delay in diagnosis of around capillaries, increased collageni- PFT was observed in 10 patients – 7
2.275±2.09 years. Clinical manifesta- sation in dermis) in all patients, non- amongst these had abnormalities on CT
tions of patients are described in Table specific inflammatory infiltrate in der- chest; in 2 CT was normal; CT could
I. Of the 22 patients with overlap scle- mis in 1 and positive lupus band test in not be done in 1. Ground glass opacities
roderma, 8 had SLE, 17 had JDM, 6 1. Dermatoscopy or nail-fold capillaros- and honeycombing were the common-
had JIA and 1 had polymyositis. Eight copy examination could be performed est abnormalities found on CT chest.
of these patients in overlap scleroderma in 25 patients and showed variable ab- Majority of patients had abnormalities
group had features suggestive of an normalities (tortuous and dilated capil- on CT at time of initial presentation
overlap of more than 1 rheumatological lary loops, capillary drop outs, avascu- (11/13, 84.6%), while 2 patients showed
disorder. lar areas and haemorrhages) (Fig. 1B). abnormalities on follow-up. One of
RP was noted in all patients and was Lung involvement was seen in 16/40 these patients had normal imaging at
recorded at presentation itself in 26/40 (40%) patients. While 4 amongst these baseline and developed ILD at 2 years
(65%) patients. RP was the sole pre- had dyspnea on exertion, others were of follow-up while he was on weekly
senting clinical manifestation in 20% detected when they were screened methotrexate therapy. In this boy, FVC
of patients. Skin tightness as present- using PFT and/or CT chest. FVC re- showed progressive worsening despite
ing symptom was noted in 26/40 (65%) vealed mild restriction in 14/40 (35%) improvement in skin score. Repeat im-
patients while all 40/40 (100%) patients patients; moderate/moderately severe aging, carried out at 2 years of follow-
developed skin tightness at some point restriction in 7/40 (17%) patients; and up, showed changes suggestive of ILD.
of their disease course. All patients had severe restriction in 3/40 (8%) patients. Second patient had poor compliance
diffuse SSc. While majority of patients with abnor- to methotrexate therapy and presented
Clinical and Experimental Rheumatology 2021 S-151Juvenile systemic scleroderma / A.K. Jindal et al.
Table III. Comparison of clinical profile between patients with systemic sclerosis with and were used in one patient because of
without features of overlap. diffuse alveolar haemorrhage. No other
Clinical manifestations SSc without overlap SSc with overlap p-value*
biological therapy was used and none
(n=18) (n=22) of the patients was ever considered for
haematopoietic stem cell transplant.
Mean age at onset of symptoms (years) 7.94 ± 3.17 7.59 ± 3.23 0.73 Six patients (15%) in our cohort died
Mean age at diagnosis (years) 10.55 ± 2.81 9.59 ± 2.15 0.22
Mean delay in diagnosis (years) 2.61 ± 1.975 2 ± 2.18 0.36 on follow-up. Cause of death was pneu-
Calcinosis 4/18 (22.2%) 6/22 (27.2%) 1 monia in 2 patients (1 of them also had
Sclerodactyly 15/18 (83.3%) 18/22 (81.8%) 1 pneumothorax; while another one had
Cutaneous ulcers 10/18 (55.5%) 4/22 (18.2%) 0.01 Streptococcus pneumoniae positivity
Lung involvement 9/18 (50%) 7/22 (31.8%) 0.33
PAH 3/18 (16.6%) 2/22 (9.1%) 0.15 in blood culture) and diffuse alveolar
Esophageal involvement 5/18 (27.7%) 3/22 (13.6%) 0.43 haemorrhage in 1 patient (he also had
Myositis 0/18 (0%) 15/22 (68.2%) 0.000 overlap with SLE and lupus nephritis).
Arthritis 3/18 (16.6%) 7/22 (31.8%) 0.27
One patient had sudden death at home
ANA positivity 16/18 (88.8%) 18/21 (85.7%) 0.67
possibly because of arrhythmia. She
Treatment also had ILD that failed to respond to
Oral prednisolone 4/18 (22.2%) 18/22 (81.8%)Juvenile systemic scleroderma / A.K. Jindal et al.
features of overlap were compared. Table IV. Comparison of clinical profile between patients with scleroderma and mortality
(Table III) There was no significant dif- vs. patients with scleroderma and no mortality.
ference in mean age of symptom onset, Clinical manifestations Patients with Patients with p-value
mean age at diagnosis and mean de- scleroderma and scleroderma and
lay in diagnosis between the 2 groups. mortality (n=6) no mortality (n=34)
Patients without overlap had higher
Mean age at onset of symptoms (years) 8.16 (4.87-11) 8 (4.75-10.12) 0.84
incidence of cutaneous ulcers as com- Mean age at diagnosis (years) 10 (7.5-15.25) 10 (8-12) 0.75
pared to patients with overlap (55% Mean delay in diagnosis (years) 2 (0.87-4.87) 1.5 (1-2.25) 0.58
vs. 18%; p-value: 0.01). Incidence of Calcinosis 0/6 (0%) 11/34 (32.3%) 0.10
all other clinical manifestations and Cutaneous ulcers 2/6 (33%) 14/34 (41.1%) 0.92
organ complications was comparable Lung involvement 2/6 (33%) 14/34 (41.1%) 0.71
PAH 2/6 (33%) 3/34 (8.8%) 0.10
between the 2 groups (Table III). Pa- Esophageal involvement 0/6 (0%) 8/34 (23.5%) 0.18
tients with overlap were given signifi- Myositis 3/6 (50%) 12/34 (35.3%) 0.49
cantly higher oral prednisolone (81% Arthritis 2/6 (33%) 8/34 (23.5%) 0.60
vs. 22%), methotrexate (72% vs. 38%) ANA positivity 6/6 (100%) 28/34 (82.3%) 0.30
and hydroxychloroquine (54% vs. 5%) Treatment
as compared to patients without over- Oral prednisolone 5/6 (83%) 17/34 (50%) 0.13
lap while cyclophosphamide (13% vs. Intravenous methylprednisolone pulse 2/6 (33%) 2/34 (5.9%) 0.03
Intravenous dexamethasone 0/6 (0%) 2/34 (5.9%) 0.54
44%) and azathioprine (9% vs. 44%) Methotrexate 3/6 (50%) 20/34 (58.8%) 0.68
was less frequently used in overlap Cyclophosphamide pulses 3/6 (50%) 8/34 (23.5%) 0.18
group as compared to patients without Azathioprine 2/6 (33%) 8/34 (23.5%) 0.60
overlap. There was no significant dif- Hydroxychloroquine 2/6 (33%) 11/34 (32.3%) 0.96
ference in mortality rate in the 2 groups.
The Kaplan-Meier survival curve of 2 To the best of our knowledge, the pre- could be the reason for this apparent
groups showed no statistically signifi- sent study on 40 patients with JSSc is difference.
cant difference in the survival (p-value the largest reported single-centre cohort Gastrointestinal manifestations were
0.586) (Fig. 2A). Similarly, there was from any developing country. seen in only 8 patients (20%). This fig-
no statistically significant difference in Mean age at symptom onset (7.5 years) ure is much lower than what has been
the survival curve of patients with or in our cohort was less as compared to reported previously (2, 4, 6, 8, 11-13,
without ILD (p-value 0.992) (Fig. 2B). several other series previously reported 15) (Table V). It may be noted that pre-
Clinical profile was compared between in the literature (8-14 years in different emptive screening for gastro-oesopha-
patients with scleroderma and mortality studies) (2, 5-15). It is possible that dis- geal reflux was not carried out in our
versus patients with scleroderma and no ease onset of JSSc in patients in North cohort.
mortality (Table IV). There was no sig- India is earlier than their counterparts Patients with JSSc may develop a varie-
nificant difference in the 2 groups ex- in West. However, this remains a con- ty of cardiac complications (28). In our
cept that significantly more patients in jecture as our numbers are small. Fur- series, we found PAH in 5 patients but
the first group were given methylpred- ther, the mean interval between onset none amongst these had cardiomyopa-
nisolone (33% vs. 5.9%, p-value 0.03). of symptoms and diagnosis 2.275±2.09 thy or documented cardiac arrhythmia.
years in our patients. This is much We have screened for PAH using 2-D
Discussion higher than figures reported from the echocardiography. Cardiac catheterisa-
JSSc is a rare disorder with an estimated Western countries (26, 27). This may tion has not been carried out in any of
incidence of 0.27 cases per million chil- represent lack of awareness about our patients.
dren per year in the United Kingdom. early clinical manifestations of JSSc Neurological complications are rarely
Less than 5% of all SSc cases have amongst the referring paediatricians. seen in patients with SSc (29). Only
onset in childhood (16, 19, 20). In this Proportion of patients with cutaneous one patient in our series had neuro-
study we have analysed our cohort of clinical manifestations (RP, calcinosis, logical involvement in the form of sei-
40 patients with JSSc collected over last cutaneous ulcers and infarcts) reported zures. Musculoskeletal involvement
25 years from North-West India. The in this series is similar to what has been (arthralgia/arthritis) is commonly seen
phenotype of several rheumatological reported previously (Table V). in patients with SSc (30). Patients may
disorders (such as JDM, SLE, Kawa- ILD was seen in 40% of our patients. have restriction of joint movements
saki disease and JIA) has been reported Reported incidence of ILD in JSSc has because of tightness of skin around the
to be different in India when compared ranged from 9–92% (4, 6-15). Inci- joints. Approximately 10–15% patients
with the western literature (21-24). dence of ILD seen in our study is much may also develop myositis (31). We
Moreover, the clinical presentation of higher than one previously reported found arthritis in 25% patients, while
SSc has been reported to be different in study from India (40% vs. 9%) (14). 40% patients had restriction of joint
Asians (25). Therefore, it is important Better follow-up and active screening movements because of skin tightness.
to study the phenotype of JSSc in India. for evidence of ILD in some patients Approximately 10–78% patients with
Clinical and Experimental Rheumatology 2021 S-153Table V. Review of published case series (including ≥10 patients) on juvenile systemic scleroderma.
S-154
Author/ Year/country Number of Raynaud at Calcinosis Abnormal Cutaneous ILD GI Cardiac Neurological Musculoskeletal +ve Overlap Treatment Mortality;
patients; mean presentation (%) nail-fold ulcers and (%) involvement involvement involvement involvement ANA features median
age at onset (%) capillaries infarcts (%) (%) (%) (%) (%) (%) (%) follow-up
(years) (%)
Cassidy et al. 1977, 15; NR 73 NR NR Pitting scar: 73 73 13 NR Joint: 60 57 46.6 CS 20%; NR
USA (2) 60 Muscle:27
Garty et al. 1991, 13; 6 (median) 69.2 NR NR NR 92.3 76.9 30.7 NR 53.8 NR NR NR 15.3; NR
USA (4)
Vancheeswaran et al. 27; 11.7 81 NR NR NR NR NR NR NR Limitation of joint 37 NR CS; CCB; NR
1996, UK (5) movements: 100 d-penicillamine;
Foeldvari et al. 2000, 135; 71.8 26.6 NR NR 50.3 65 45 15.5 Joints- 78.5 5.1 NR CS; MTX; HCQs; 5.9%;
multi-national (6) 10.5 Muscles- 9.6 d-penicillamine
60 months (median)
Martini et al. 2006, 153; 83 19 40 29 29 Dysphagia in Pericarditis/ Seizures in 3, Arthritis 27, 80.7; Patients with CS; MTX; Cyc; 11.8%;
Multi-nation (7) 8.1 24; GE reflux arrhythmia abnormal MRI arthralgia 36, ENA overlap CCB; ACE 30 months
in 30 in 10; heart in 3, peripheral muscle weakness in 42.5% excluded inhibitors; PPI;
failure in 7 neuropathy in 1 24 d-penicillamine
Scalapino et al. 2006, 111; NR NR NR NR NR 55 74 17 NR 82 97 29% NR 37%; 206
USA (8) months
Juvenile systemic scleroderma / A.K. Jindal et al.
Misra et al. 2007, 23; 83 NR NR 60.8 and 13 65.2 Dysphagia in NR Arthritis in 34.7 65.2 Patients CS; CCB; MTX; 4.3%;
India (9) 13 (diffuse) respectively 30.4; GE with HCQs; Cyc; 34 months
10 (limited) reflux in 34.7 overlap d-penicillamine; (mean)
[Both median] excluded sildenafil
Foeldvari et al. 2010, 52; 100 NR NR NR 22 NR 3 NR NR 75; ENA 37 CS; MTX; Cyc; 27%;
Germany (10) 14 in 52% Aza; MMF; 108 months
cyclosporine; (mean)
IVIg; ATG
transplant;
Foeldvari et al. 2012, 60; 95 NR NR 35.6 23.3 Esophagus 60 PAH in 13.6 NR Arthritis 10, 90 9 NR None; NR
Multi-nation (11) 12.2 Stomach 16.7 contractures30,
Intestine 15 muscle
weakness 20
Boroweic et al. 2012, 15; 86.7 NR 66.7 40 86* 46.7 *LV NR NR 60 NR NR 7.3%;
Poland (12) 8 hypertrophy 20; 123 months
LA enlargement 7; (mean)
PAH 35; Wide
IVC 23; AV
block 7; Sinus
tachycardia 14
Hatta et al. 2014, 11; NR 9.1 NR 90.9 9.1 36.7 PAH 9.1 NR Joint ** NR NR none;68.4
Japan (13) 9.4 involvement 27.3 months (mean)
Bagri et al. 2017, 32; 68.7 NR NR 18.7 and 3.7 9.3 9.3 NR NR Arthritis or 50 31.2 CS; MTX; None;
India (14) 9.4 respectively arthralgia in 50, dexa; CCB; 19.7 months
muscle PPI; HCQs;
weakness 31 sildenafil
Stevens et al. 2018, 64; 10.3 73 10 70 46 34 42 2 NR Arthritis 19, 84 6.2 CS; MTX; Cyc; None; 14.52
USA (15) contractures 34, Sulfasalazine; months
myositis 12 HCQs; MMF;
IVIG; etanercept;
abatacept
Present study, India 40; 7.75 years 26/40 (65%) 10/40 (25%) 17/17 (100%) Ulcers: 40% 8/40 (20%) PAH in 5/40 1 patient had Arthritis in 10/40 34/39 22/40 CS; MTX; dexa; 6/40 (15%);
14/40 (35%), (12.5%) seizures (25%), restriction (87.1%) (55%) CCB; PPI; HCQs; 51.7 months
gangrene in of joint movements Cyc; Aza; MMF (mean)
2/40 (5%) due to tight skin sildenafil;
16/40 (40%) Rituximab
ACE: angiotensin convertase enzyme; ANA: antinuclear antibody; ATG: anti-thymocyte globulin; Aza: azathioprine; CCB: calcium channel blockers; CS: corticosteroids; Cyc: cyclophosphamide; dexa: pulse dexamethasone; ENA: extractable nuclear antigen;
F/U: follow-up; GI: gastrointestinal; HCQs: hydroxychloroquine; ILD: interstitial lung disease; ??: inferior vena cava; IVIg: intravenous immunoglobulin; LA: left atrium; LV: left ventricular; MMF: mycophenolate mofetil; MRI: magnetic resonance imaging;
MTX: methotrexate; NR: not reported; PAH: pulmonary artery hypertension; PPI: proton pump inhibitors.
*Probable referral bias as this study was carried out in a cardiology unit and patients were evaluated for specifically and extensively valuated for cardiovascular complications.
**Anti-topoisomerase 1 antibody in 90.9% and anti U1RNP in 9.1%.
Clinical and Experimental Rheumatology 2021Juvenile systemic scleroderma / A.K. Jindal et al.
JSSc have been reported to have arthri- somerase I antibody was not positive in all patients at diagnosis and then at
tis (Table V). in any of the 18 patients in whom this regular intervals to correlate with the
ANA positivity was seen in 87% pa- was tested. It may be important to care- disease activity. Six-minute walk test
tients in our cohort. These results are fully look at clinical features of other and diffusion capacity of lung for car-
similar to previously published data overlapping diseases with JSSc as this bon monoxide (DLCO) was not carried
from other centres (Table V). It is known has been found to impact the therapeu- out. We have not used biologics in any
that approximately 6% patients of JSSc tic decisions (35). of our patients except rituximab in 1.
may be ANA negative (32). It has also Two patients in the present series had
been shown that ANA negative SSc pa- abnormal PFT (moderate restriction) Conclusion
tients constitute a different sub-group of but CT chest showed no abnormalities. JSSc is a rare childhood rheumatic dis-
the disease. They are more likely to be There may be several reasons for this ease and limited form of SSc is even
male, are at higher risk of gastrointesti- discrepancy. These include: 1. Falla- rarer in children. Overlap with other
nal involvement and have lesser chances cies in the interpretation of FVC val- rheumatic diseases is more common
of cutaneous vasculopathy as compared ues in young children (technical error); in children with SSc as compared to
to ANA positive SSc patients (33). None 2. False positivity for FVC in patients adults. Children in our cohort were
of the patients with ANA negativity in with SSc that could be because of tight- younger at disease onset as compared to
our series had gastrointestinal involve- ening of skin of chest and abdominal many other previously reported cohorts.
ment, 2/5 (40%) had ILD and male to wall; tightening of skin around the oral Even though mortality in patients with
female ratio was 2:3. aperture and atrophy of accessory mus- SSc has markedly reduced in last few
Published literature of JSSc shows cles (36-39). years, infections would remain a signifi-
that JSSc overlap occurs in 6–46% of Therapy used for treatment of our pa- cant concern in developing countries.
patients (Table V). Our results were tients was largely similar to what has
largely similar, with overlap occurring been used in the literature (Table V). References
in 55% patients. Common rheumato- However, we have not used cyclo- 1. ZULIAN F, WOO P, ATHREYA BH et al.: The
Pediatric Rheumatology European Society/
logic diseases that have been reported sporine, anti-thymocyte globulin (ATG) American College of Rheumatology/Europe-
to have overlap with SSc include JDM, and biologics (except rituximab in 1). an League against Rheumatism provisional
SLE, JIA or rheumatoid arthritis and Our study is the largest follow-up study classification criteria for juvenile systemic
primary Sjögren’s syndrome (33, 34). on JSSc from India with a mean follow- sclerosis. Arthritis Rheum 2007; 57: 203-12.
2. CASSIDY JT, SULLIVAN DB, DABICH L, PET-
No patient in the present study had pri- up of 51.7 months (and total follow-up TY RE: Scleroderma in children. Arthritis
mary Sjögren’s syndrome. of 2070 patient months). Mortality rate Rheum 1977; 20 (Suppl.): 351-4.
A study by Foocharoen et al. compared of 15% in our cohort is higher than re- 3. ORLANDI M, LEPRI G, DAMIANI A et al.:
One year in review 2020: systemic sclerosis.
the clinical profile of adult SSc patients cently reported mortality in patients
Clin Exp Rheumatol 2020; 38 (Suppl. 125):
with or without features of overlap with SSc from various other centres S3-17.
(34). It was found that mean age of pa- (Table V) (11-15). Most common cause 4. GARTY BZ, ATHREYA BH, WILMOTT R,
tients with features of overlap (16% of of death in children with JSSc is in- SCARPA N, DOUGHTY R, DOUGLAS SD: Pul-
monary functions in children with progres-
all patients in the cohort) was signifi- volvement of lungs, heart and kidneys. sive systemic sclerosis. Pediatrics 1991; 88:
cantly less than patients with pure scle- Reason for higher proportion of death 1161-7.
roderma. This may be one of the rea- in our series is likely because of late 5. VANCHEESWARAN R, BLACK CM, DAVID J et
sons for higher percentage of patients referrals, severe disease, infections and al.: Childhood-onset scleroderma: is it differ-
ent from adult-onset disease. Arthritis Rheum
with overlap in the present study as difficulty in accessing health care in 1996; 39: 1041-9.
ours was a paediatric cohort. It was also emergency situations. 6. FOELDVARI I, ZHAVANIA M, BIRDI N et al.:
observed by Foocharoen et al. that pa- The main strength of our study is that Favourable outcome in 135 children with ju-
tients with overlap syndrome required this is the largest reported single-centre venile systemic sclerosis: results of a multi-
national survey. Rheumatology 2000; 39:
higher doses of steroids and were more cohort of JSSc from India. We report a 556-9.
frequently anti-topoisomerase I anti- cumulative experience of 2070 patient 7. MARTINI G, FOELDVARI I, RUSSO R et al.:
body positive (34). In our cohort, pa- months in JSSc. Being a single-centre Systemic sclerosis in childhood: clinical
and immunologic features of 153 patients in
tients with overlap were similar in age study, there is uniformity in diagnosis. an international database. Arthritis Rheum
of presentation and had significantly Despite having recorded ILD in more 2006; 54: 3971-8.
less incidence of cutaneous ulcers. Pa- than 1/3rd of our patients, the overall 8. SCALAPINO K, ARKACHAISRI T, LUCAS M
tients with overlap required significant- prognosis has been reasonable. et al.: Childhood onset systemic sclerosis:
classification, clinical and serologic features,
ly higher doses of oral prednisolone, There are a few limitations of this study. and survival in comparison with adult onset
methotrexate and hydroxychloroquine We could not perform regular assess- disease. J Rheumatol 2006; 33: 1004-13.
and significantly less cyclophospha- ments of disease activity using J4S and 9. MISRA R, SINGH G, AGGARWAL P, AGGAR-
mide and azathioprine as compared mRSS - a prospective longitudinal study WAL A: Juvenile onset systemic sclerosis:
a single center experience of 23 cases from
to patients with JSSc without overlap. with repeated assessments would have Asia. Clin Rheumatol 2007; 26: 1259-62.
No difference was observed in overall been more useful. Nail fold capillaros- 10. FOELDVARI I, NIHTYANOVA SI, WIERK A,
outcome in the 2 groups. Anti-topoi- copy assessment could not be performed DENTON CP: Characteristics of patients with
Clinical and Experimental Rheumatology 2021 S-155Juvenile systemic scleroderma / A.K. Jindal et al.
juvenile onset systemic sclerosis in an adult 21. SHARMA A, GUPTA A, RAWAT A, SURI D, SIN- 2015; 41: 507-18.
single-center cohort. J Rheumatol 2010; 37: GH S: Long-term outcome in children with 31. PAIK JJ, MAMMEN AL, WIGLEY FM, GELBER
2422-6. juvenile dermatomyositis: A single-center AC: Myopathy in scleroderma, its identifi-
11. FOELDVARI I, TYNDALL A, ZULIAN F et al.: study from north India. Int J Rheum Dis cation, prevalence, and treatment: lessons
Juvenile and young adult-onset systemic 2020; 23: 392-6. learned from cohort studies. Curr Opin Rheu-
sclerosis share the same organ involvement 22. SINGH S, SURI D, AULAKH R, GUPTA A, matol 2014; 26: 124-30.
in adulthood: data from the EUSTAR data- RAWAT A, KUMAR RM: Mortality in children 32. SALAZAR G, ASSASSI S, WIGLEY F et al.:
base. Rheumatology 2012; 51: 1832-7. with juvenile dermatomyositis: two decades Antinuclear antibody negative systemic scle-
12. BOROWIEC A, DABROWSKI R, WOZNIAK J et of experience from a single tertiary care cen- rosis. Semin Arthritis Rheum 2015; 44: 680-
al.: Cardiovascular assessment of asympto- tre in North India. Clin Rheumatol 2014; 33: 6.
matic patients with juvenile-onset localized 1675-9. 33. SHARMA S, KUMAR U: Scleroderma overlap
and systemic scleroderma: 10 years prospec- 23. ABUJAM B, GUPTA A, SURI D, RAWAT A, syndromes. Int J Rheum Dis 2016; 19: 831-3.
tive observation. Scand J Rheumatol 2012; SINGH S: Trends and predictors of mortality 34. FOOCHAROEN C, NETWIJITPAN S, MAHAK-
41: 33-8. in childhood onset lupus in a single North- KANUKRAUH A, SUWANNAROJ S, NANAGA-
13. HATTA Y, HASEGAWA M, MATSUSHITA T, Indian centre over 23 years: a retrospective RA R: Clinical characteristics of scleroderma
HAMAGUCHI Y, FUJIMOTO M, TAKEHARA K: study. Clin Exp Rheumatol 2016; 34: 554-9. overlap syndromes: comparisons with pure
The clinical characteristics of juvenile-onset 24. SINGH S, KAWASAKI T: Kawasaki disease in scleroderma. Int J Rheum Dis 2016; 19: 913-
systemic sclerosis in Japanese patients. Mod India, lessons learnt over the last 20 years. 23.
Rheumatol 2014; 24: 377-9. Indian Pediatr 2016; 53: 119-24. 35. KHAOSUT P, PILKINGTON C, WEDDERBURN
14. BAGRI NK, RAJ D, KAUR J et al.: Juvenile 25. JAEGER VK, TIKLY M, XU D et al.: Racial dif- LR, COMPEYROT-LACASSAGNE S: An inter-
systemic sclerosis: experience from a tertiary ferences in systemic sclerosis disease pres- national survey of developing classification
care center from India. Rheumatol Int 2017; entation: a European Scleroderma Trials and criteria for juvenile dermatomyositis-scle-
37: 1687-91. Research group study. Rheumatology (Ox- roderma overlap. Rheumatology (Oxford)
15. STEVENS BE, TOROK KS, LI SC et al.: ford) 2020; 59: 1684-94. 2019; 58: 2062-4.
Clinical characteristics and factors associat- 26. HAWLEY DP, BAILDAM EM, AMIN TS et al.: 36. ABRAMSON MJ, BARNETT AJ, LITTLEJOHN
ed with disability and impaired quality of life Access to care for children and young peo- GO, SMITH MM, HALL S: Lung function ab-
in children with juvenile systemic sclerosis. ple diagnosed with localized scleroderma or normalities and decline of spirometry in
Arthritis Care Res 2018; 70: 1806-13. juvenile SSc in the UK. Rheumatology (Ox- scleroderma: an overrated danger? Postgrad
16. HERRICK AL, ENNIS H, BHUSHAN M, ford) 2012; 51: 1235-9. Med J 1991; 67: 632-7.
SILMAN AJ, BAILDAM EM: Incidence of 27. DISTLER O, ALLANORE Y, DENTON CP et 37. AGUAYO SM, RICHARDSON CL, ROMAN J:
childhood linear scleroderma and systemic al.: Factors influencing early referral, early Severe extrapulmonary thoracic restriction
sclerosis in the UK and Ireland. Arthritis diagnosis and management in patients with caused by morphea, a form of localized scle-
Care Res 2010; 62: 213-8. diffuse cutaneous systemic sclerosis. Rheu- roderma. Chest 1993; 104: 1304-5.
17. CZIRJÁK L, FOELDVARI I, MÜLLER-LADNER matology (Oxford) 2018; 57: 813-7. 38. NAWATA T, SHIRAI Y, SUZUKI M, KUWANA
U: Skin involvement in systemic sclerosis. 28. LAMBOVA S: Cardiac manifestations in sys- M: Chest wall muscle atrophy as a contribu-
Rheumatology (Oxford) 2008; 47 (Suppl. 5): temic sclerosis. World J Cardiol 2014; 6: tory factor for forced vital capacity decline in
v44-45. 993-1005. systemic sclerosis-associated interstitial lung
18. LA TORRE F, MARTINI G, RUSSO R et al.: 29. AMARAL TN, PERES FA, LAPA AT, MARQUES- disease. Rheumatology (Oxford) 2021; 60:
A preliminary disease severity score for ju- NETO JF, APPENZELLER S: Neurologic in- 250-55.
venile systemic sclerosis. Arthritis Rheum volvement in scleroderma: a systematic re- 39. SULIMAN YA, DOBROTA R, HUSCHER D et
2012; 64: 4143-50. view. Semin Arthritis Rheum 2013; 43: 335- al.: Brief report: Pulmonary function tests:
19. ZULIAN F: Scleroderma in children. Best 47. high rate of false-negative results in the early
Pract Res Clin Rheumatol 2017; 31: 576-95. 30. MORRISROE KB, NIKPOUR M, PROUDMAN detection and screening of scleroderma-re-
20. FOELDVARI I: Update on juvenile systemic SM: Musculoskeletal manifestations of sys- lated interstitial lung disease. Arthritis Rheu-
sclerosis. Curr Rheumatol Rep 2015; 17: 18. temic sclerosis. Rheum Dis Clin North Am matol 2015; 67: 3256-61.
S-156 Clinical and Experimental Rheumatology 2021You can also read
