pág. 9801
SYSTEMIC SCLEROSIS IN A PRESCHOOL-AGED
PATIENT: AN UNUSUALLY EARLY
PRESENTATION OF AN AUTOIMMUNE DISEASE
ESCLEROSIS SISTÉMICA EN UN PACIENTE EN EDAD
PREESCOLAR: UNA MANIFESTACIÓN INUSUALMENTE
TEMPRANA DE UNA ENFERMEDAD AUTOIMMUNE
Melissa Carrillo Hernández
Hospital General ISSSTE
Braulio Esteban López Reyes
Hospital General ISSSTE
Karime Giselle Sandoval Enriquez
Hospital General ISSSTE
Daniela Nicolle Gómez Narváez
Hospital General ISSSTE
Gloria Jimena Coello Uribe
Hospital General ISSSTE
pág. 9802
DOI: https://doi.org/10.37811/cl_rcm.v9i4.19547
Systemic Sclerosis in a Preschool-Aged Patient: An Unusually Early
Presentation of an Autoimmune Disease
Melissa Carrillo Hernández1
dra.melissa44carrillo@gmail.com
https://orcid.org/0009-0002-5196-1269
Hospital General ISSSTE Aguascalientes,
Servicio de Medicina Interna, Aguascalientes,
México.
Braulio Esteban López Reyes
brauliol.reyes1203@gmail.com
https://orcid.org/0009-0003-3547-2243
Hospital General ISSSTE Aguascalientes,
Servicio de Pediatría, Aguascalientes, México.
Karime Giselle Sandoval Enriquez
kgse1124@gmail.com
https://orcid.org/0009-0003-4952-7209
Departamento de Medicina, Universidad
Cuauhtémoc Plantel Aguascalientes, México
Daniela Nicolle Gómez Narváez
dra.nicollegomez@gmail.com
https://orcid.org/0009-0004-7086-1858
Hospital General ISSSTE Aguascalientes,
Servicio de Cirugía General, Aguascalientes,
México.
Gloria Jimena Coello Uribe
jimena_coello@hotmail.com
https://orcid.org/0009-0000-7659-1546
Hospital General ISSSTE Aguascalientes,
Servicio de Cirugía General, Aguascalientes,
México.
ABSTRACT
Introduction: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by skin fibrosis,
vascular alterations, and specific autoantibodies. Onset during childhood is uncommon, and presentation
at preschool age is exceptional. Case report: We describe an 8-year-old female presenting with a
progressive indurated plaque on the left leg, refractory to topical treatments. Laboratory tests revealed
positive antinuclear antibodies (ANA) and anti-topoisomerase I (Scl-70). Skin biopsy demonstrated
epidermal atrophy and dermal sclerosis consistent with scleroderma. Nailfold capillaroscopy showed a
scleroderma pattern, while chest CT, pulmonary function tests, and echocardiography revealed no
visceral involvement. A diagnosis of juvenile systemic sclerosis was established. Methotrexate therapy
was initiated, along with multidisciplinary follow-up, leading to clinical stabilization at six months.
Discussion: Pediatric SSc accounts for less than 5% of all cases, with localized morphea being the most
common subtype. Systemic disease at preschool age is exceedingly rare and poses diagnostic challenges.
Capillaroscopy and systemic screening are essential for assessing progression risk. Methotrexate is
considered first-line therapy in children, although long-term follow-up is mandatory to detect
cardiopulmonary complications. Conclusions: This case contributes to the international literature by
documenting an unusual presentation of SSc in preschool age, highlighting the importance of early
diagnosis, immunomodulatory therapy, and multidisciplinary management.
Keywords: systemic sclerosis, pediatrics, autoimmunity, capillaroscopy, methotrexate.
1 Autor principal
Correspondencia: dra.melissa44carrillo@gmail.com
DOI: https://doi.org/10.37811/cl_rcm.v9i4.19547
Systemic Sclerosis in a Preschool-Aged Patient: An Unusually Early
Presentation of an Autoimmune Disease
Melissa Carrillo Hernández1
dra.melissa44carrillo@gmail.com
https://orcid.org/0009-0002-5196-1269
Hospital General ISSSTE Aguascalientes,
Servicio de Medicina Interna, Aguascalientes,
México.
Braulio Esteban López Reyes
brauliol.reyes1203@gmail.com
https://orcid.org/0009-0003-3547-2243
Hospital General ISSSTE Aguascalientes,
Servicio de Pediatría, Aguascalientes, México.
Karime Giselle Sandoval Enriquez
kgse1124@gmail.com
https://orcid.org/0009-0003-4952-7209
Departamento de Medicina, Universidad
Cuauhtémoc Plantel Aguascalientes, México
Daniela Nicolle Gómez Narváez
dra.nicollegomez@gmail.com
https://orcid.org/0009-0004-7086-1858
Hospital General ISSSTE Aguascalientes,
Servicio de Cirugía General, Aguascalientes,
México.
Gloria Jimena Coello Uribe
jimena_coello@hotmail.com
https://orcid.org/0009-0000-7659-1546
Hospital General ISSSTE Aguascalientes,
Servicio de Cirugía General, Aguascalientes,
México.
ABSTRACT
Introduction: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by skin fibrosis,
vascular alterations, and specific autoantibodies. Onset during childhood is uncommon, and presentation
at preschool age is exceptional. Case report: We describe an 8-year-old female presenting with a
progressive indurated plaque on the left leg, refractory to topical treatments. Laboratory tests revealed
positive antinuclear antibodies (ANA) and anti-topoisomerase I (Scl-70). Skin biopsy demonstrated
epidermal atrophy and dermal sclerosis consistent with scleroderma. Nailfold capillaroscopy showed a
scleroderma pattern, while chest CT, pulmonary function tests, and echocardiography revealed no
visceral involvement. A diagnosis of juvenile systemic sclerosis was established. Methotrexate therapy
was initiated, along with multidisciplinary follow-up, leading to clinical stabilization at six months.
Discussion: Pediatric SSc accounts for less than 5% of all cases, with localized morphea being the most
common subtype. Systemic disease at preschool age is exceedingly rare and poses diagnostic challenges.
Capillaroscopy and systemic screening are essential for assessing progression risk. Methotrexate is
considered first-line therapy in children, although long-term follow-up is mandatory to detect
cardiopulmonary complications. Conclusions: This case contributes to the international literature by
documenting an unusual presentation of SSc in preschool age, highlighting the importance of early
diagnosis, immunomodulatory therapy, and multidisciplinary management.
Keywords: systemic sclerosis, pediatrics, autoimmunity, capillaroscopy, methotrexate.
1 Autor principal
Correspondencia: dra.melissa44carrillo@gmail.com
pág. 9803
Esclerosis sistémica en un paciente en edad preescolar: una manifestación
inusualmente temprana de una enfermedad autoimmune
RESUMEN
Introducción: La esclerosis sistémica (ES) es una enfermedad autoinmune poco frecuente caracterizada
por fibrosis cutánea, alteraciones vasculares y autoanticuerpos específicos. Su aparición durante la
infancia es poco habitual, y su presentación en edad preescolar es excepcional. Caso clínico:
Describimos el caso de una niña de 8 años que presentaba una placa indurada progresiva en la pierna
izquierda, refractaria a los tratamientos tópicos. Las pruebas de laboratorio revelaron anticuerpos
antinucleares (ANA) y anti-topoisomerasa I (Scl-70) positivos. La biopsia cutánea mostró atrofia
epidérmica y esclerosis dérmica compatibles con esclerodermia. La capilaroscopia del lecho ungueal
mostró un patrón de esclerodermia, mientras que la TC torácica, las pruebas de función pulmonar y la
ecocardiografía no revelaron afectación visceral. Se estableció un diagnóstico de esclerosis sistémica
juvenil. Se inició un tratamiento con metotrexato, junto con un seguimiento multidisciplinar, lo que
condujo a la estabilización clínica a los seis meses. Discusión: La esclerosis sistémica pediátrica
representa menos del 5 % de todos los casos, siendo la morfea localizada el subtipo más común. La
enfermedad sistémica en edad preescolar es extremadamente rara y plantea dificultades diagnósticas. La
capilaroscopia y el cribado sistémico son esenciales para evaluar el riesgo de progresión. El metotrexato
se considera el tratamiento de primera línea en niños, aunque es obligatorio realizar un seguimiento a
largo plazo para detectar complicaciones cardiopulmonares. Conclusiones: Este caso contribuye a la
literatura internacional al documentar una presentación inusual de la ES en edad preescolar, lo que
destaca la importancia del diagnóstico precoz, el tratamiento inmunomodulador y el manejo
multidisciplinario.
Palabras clave: esclerosis sistémica, pediatría, autoinmunidad, capilaroscopia, metotrexato
Artículo recibido 20 julio 2025
Aceptado para publicación: 20 agosto 2025
Esclerosis sistémica en un paciente en edad preescolar: una manifestación
inusualmente temprana de una enfermedad autoimmune
RESUMEN
Introducción: La esclerosis sistémica (ES) es una enfermedad autoinmune poco frecuente caracterizada
por fibrosis cutánea, alteraciones vasculares y autoanticuerpos específicos. Su aparición durante la
infancia es poco habitual, y su presentación en edad preescolar es excepcional. Caso clínico:
Describimos el caso de una niña de 8 años que presentaba una placa indurada progresiva en la pierna
izquierda, refractaria a los tratamientos tópicos. Las pruebas de laboratorio revelaron anticuerpos
antinucleares (ANA) y anti-topoisomerasa I (Scl-70) positivos. La biopsia cutánea mostró atrofia
epidérmica y esclerosis dérmica compatibles con esclerodermia. La capilaroscopia del lecho ungueal
mostró un patrón de esclerodermia, mientras que la TC torácica, las pruebas de función pulmonar y la
ecocardiografía no revelaron afectación visceral. Se estableció un diagnóstico de esclerosis sistémica
juvenil. Se inició un tratamiento con metotrexato, junto con un seguimiento multidisciplinar, lo que
condujo a la estabilización clínica a los seis meses. Discusión: La esclerosis sistémica pediátrica
representa menos del 5 % de todos los casos, siendo la morfea localizada el subtipo más común. La
enfermedad sistémica en edad preescolar es extremadamente rara y plantea dificultades diagnósticas. La
capilaroscopia y el cribado sistémico son esenciales para evaluar el riesgo de progresión. El metotrexato
se considera el tratamiento de primera línea en niños, aunque es obligatorio realizar un seguimiento a
largo plazo para detectar complicaciones cardiopulmonares. Conclusiones: Este caso contribuye a la
literatura internacional al documentar una presentación inusual de la ES en edad preescolar, lo que
destaca la importancia del diagnóstico precoz, el tratamiento inmunomodulador y el manejo
multidisciplinario.
Palabras clave: esclerosis sistémica, pediatría, autoinmunidad, capilaroscopia, metotrexato
Artículo recibido 20 julio 2025
Aceptado para publicación: 20 agosto 2025
pág. 9804
INTRODUCTION
Systemic sclerosis (SSc) is a chronic, multisystem autoimmune disease characterized by cutaneous
fibrosis, vascular abnormalities, and the presence of specific autoantibodies against nuclear and
cytoplasmic antigens1. Although its pathogenesis is not fully understood, it is recognized as the result of
interactions among genetic, epigenetic, immunological, and environmental factors2,3.
SSc is considered a rare disease, with an estimated prevalence ranging from 7 to 489 cases per million
inhabitants and an annual incidence varying from 0.6 to 122 cases per million, with significant
geographic differences1,4. The average age of onset is between 30 and 50 years, with a clear female
predominance5.
In the pediatric population, systemic sclerosis is extremely rare. Fewer than 5% of cases occur before
the age of 16, and when it does, it usually manifests as localized scleroderma in the form of morphea,
while the systemic variant at preschool age is even less common6,7,8. These cases pose diagnostic and
therapeutic challenges due to the lack of validated clinical criteria for children and the limited cumulative
experience available in the literature9.
The prognosis of SSc largely depends on visceral involvement, particularly cardiopulmonary disease.
Complications such as pulmonary hypertension and interstitial lung fibrosis account for most of the
mortality, which may be up to eight times higher than in the general population10,11.
The present report describes a case of systemic sclerosis in a preschool-aged patient, representing a
particularly unusual manifestation of the disease and contributing to the available literature on this entity
in childhood.
Case Presentation
We report the case of an 8-year-old female patient, originally and resident of Mexico. She was the third
child of a pregnancy complicated by maternal gestational diabetes, delivered via cesarean section at 38
weeks of gestation, with a birth weight of 3100 gr and length of 50 cm, both appropriate for gestational
age. Psychomotor development was normal, and immunizations were up to date for age.
INTRODUCTION
Systemic sclerosis (SSc) is a chronic, multisystem autoimmune disease characterized by cutaneous
fibrosis, vascular abnormalities, and the presence of specific autoantibodies against nuclear and
cytoplasmic antigens1. Although its pathogenesis is not fully understood, it is recognized as the result of
interactions among genetic, epigenetic, immunological, and environmental factors2,3.
SSc is considered a rare disease, with an estimated prevalence ranging from 7 to 489 cases per million
inhabitants and an annual incidence varying from 0.6 to 122 cases per million, with significant
geographic differences1,4. The average age of onset is between 30 and 50 years, with a clear female
predominance5.
In the pediatric population, systemic sclerosis is extremely rare. Fewer than 5% of cases occur before
the age of 16, and when it does, it usually manifests as localized scleroderma in the form of morphea,
while the systemic variant at preschool age is even less common6,7,8. These cases pose diagnostic and
therapeutic challenges due to the lack of validated clinical criteria for children and the limited cumulative
experience available in the literature9.
The prognosis of SSc largely depends on visceral involvement, particularly cardiopulmonary disease.
Complications such as pulmonary hypertension and interstitial lung fibrosis account for most of the
mortality, which may be up to eight times higher than in the general population10,11.
The present report describes a case of systemic sclerosis in a preschool-aged patient, representing a
particularly unusual manifestation of the disease and contributing to the available literature on this entity
in childhood.
Case Presentation
We report the case of an 8-year-old female patient, originally and resident of Mexico. She was the third
child of a pregnancy complicated by maternal gestational diabetes, delivered via cesarean section at 38
weeks of gestation, with a birth weight of 3100 gr and length of 50 cm, both appropriate for gestational
age. Psychomotor development was normal, and immunizations were up to date for age.
pág. 9805
Family history
The mother had a history of type 2 diabetes mellitus and systemic arterial hypertension. The maternal
grandparents had oncological histories (gastric and stomach cancer), and the paternal grandfather had
pancreatic cancer. The father had no known chronic illnesses.
Personal history
The patient denied medication allergies, genetic conditions, or chronic diseases. There was no history
of recurrent infections or previous hospitalizations.
History of present illness
At 8 years of age, her mother noticed the appearance of an indurated skin lesion on the anterior aspect
of the left leg, measuring approximately 5 cm in diameter, non-painful, without erythema or associated
systemic symptoms. The lesion gradually progressed in size over the following months, despite multiple
topical treatments prescribed by different physicians (including corticosteroids, emollients, and topical
antibiotics) without improvement, which led to referral for pediatric dermatology evaluation.
Physical examination
Dermatological examination revealed a localized dermatosis on the anterior surface of the left leg,
characterized by an indurated plaque measuring 10 × 7 cm, with a rough, shiny surface, light brown
hyperpigmentation, loss of skin elasticity, and difficulty in pinching the lesion. There was no tenderness
on palpation or local inflammatory signs. No additional cutaneous lesions or mucosal abnormalities
were identified. Facial telangiectasias and Raynaud’s phenomenon were not observed at that time.
Family history
The mother had a history of type 2 diabetes mellitus and systemic arterial hypertension. The maternal
grandparents had oncological histories (gastric and stomach cancer), and the paternal grandfather had
pancreatic cancer. The father had no known chronic illnesses.
Personal history
The patient denied medication allergies, genetic conditions, or chronic diseases. There was no history
of recurrent infections or previous hospitalizations.
History of present illness
At 8 years of age, her mother noticed the appearance of an indurated skin lesion on the anterior aspect
of the left leg, measuring approximately 5 cm in diameter, non-painful, without erythema or associated
systemic symptoms. The lesion gradually progressed in size over the following months, despite multiple
topical treatments prescribed by different physicians (including corticosteroids, emollients, and topical
antibiotics) without improvement, which led to referral for pediatric dermatology evaluation.
Physical examination
Dermatological examination revealed a localized dermatosis on the anterior surface of the left leg,
characterized by an indurated plaque measuring 10 × 7 cm, with a rough, shiny surface, light brown
hyperpigmentation, loss of skin elasticity, and difficulty in pinching the lesion. There was no tenderness
on palpation or local inflammatory signs. No additional cutaneous lesions or mucosal abnormalities
were identified. Facial telangiectasias and Raynaud’s phenomenon were not observed at that time.
pág. 9806
Figure 1. Clinical examination of the right lower
limb showing soft edema on the thigh with
evident pitting on digital pressure.
Figure 2. Same limb at rest, showing mild diffuse
erythema and persistence of proximal edema.
General physical examination showed weight and height appropriate for age, blood pressure of 90/60
mmHg, heart rate of 88 bpm, respiratory rate of 18 breaths per minute, and temperature of 36.7 °C. No
signs of respiratory or cardiovascular involvement were observed on initial examination.
Figure 1. Clinical examination of the right lower
limb showing soft edema on the thigh with
evident pitting on digital pressure.
Figure 2. Same limb at rest, showing mild diffuse
erythema and persistence of proximal edema.
General physical examination showed weight and height appropriate for age, blood pressure of 90/60
mmHg, heart rate of 88 bpm, respiratory rate of 18 breaths per minute, and temperature of 36.7 °C. No
signs of respiratory or cardiovascular involvement were observed on initial examination.
pág. 9807
Figure 3. Nail evaluation under dermoscopy
revealing periungual inflammatory changes and a
small lateral fissure.
Figure 4. Magnified view of the nail
demonstrating mild hyperkeratosis of the
proximal nail fold and periungual groove,
consistent with chronic inflammatory
involvement.
Figure 3. Nail evaluation under dermoscopy
revealing periungual inflammatory changes and a
small lateral fissure.
Figure 4. Magnified view of the nail
demonstrating mild hyperkeratosis of the
proximal nail fold and periungual groove,
consistent with chronic inflammatory
involvement.
pág. 9808
Imaging and complementary studies
● Skin biopsy: a 0.9 × 4 cm specimen from the left leg showed focal epidermal atrophy,
hyalinization and dermal sclerosis, with adnexal atrophy, consistent with scleroderma.
● Nailfold capillaroscopy: demonstrated decreased capillary density with avascular areas and the
presence of megacapillaries, findings compatible with a scleroderma pattern.
● Plain radiograph of the left leg: no evidence of calcinosis or bone involvement.
● High-resolution chest CT (HRCT): no evidence of interstitial lung fibrosis.
● Transthoracic echocardiogram: preserved ventricular function, no estimated pulmonary
hypertension.
● Pulmonary function tests: within normal parameters for age.
Clinical course and management
Based on the clinical, serological, and histopathological findings, a diagnosis of juvenile systemic
sclerosis, localized form with risk of systemic progression, was established. The case was discussed
with pediatric rheumatology, and treatment with oral methotrexate at 10 mg/m²/week was initiated,
along with folic acid supplementation and photoprotection measures. Multidisciplinary follow-up was
recommended, including periodic cardiopulmonary evaluations for early detection of complications.
Laboratory studies
Initial laboratory tests revealed the following:
Immunologic profile:
● Complete blood count: hemoglobin
12.4 g/dL, leukocytes 6,500/μL, platelets
280,000/μL.
● Serum chemistry: glucose 88 mg/dL,
urea 28 mg/dL, creatinine 0.5 mg/dL.
● Liver function tests: AST 25 U/L, ALT
21 U/L, ALP 180 U/L.
● Erythrocyte sedimentation rate: 36
mm/h.
● C-reactive protein: 1.2 mg/dL.
● ANA positive, speckled pattern, at a titer
of 1:320.
● Anti–topoisomerase I (Scl-70)
antibodies positive.
● Anti-centromere antibodies negative.
● Anti-Smith and anti-RNP antibodies
negative.
● Rheumatoid factor and anti-CCP
antibodies negative.
● Complement C3 and C4 within normal
ranges.
Imaging and complementary studies
● Skin biopsy: a 0.9 × 4 cm specimen from the left leg showed focal epidermal atrophy,
hyalinization and dermal sclerosis, with adnexal atrophy, consistent with scleroderma.
● Nailfold capillaroscopy: demonstrated decreased capillary density with avascular areas and the
presence of megacapillaries, findings compatible with a scleroderma pattern.
● Plain radiograph of the left leg: no evidence of calcinosis or bone involvement.
● High-resolution chest CT (HRCT): no evidence of interstitial lung fibrosis.
● Transthoracic echocardiogram: preserved ventricular function, no estimated pulmonary
hypertension.
● Pulmonary function tests: within normal parameters for age.
Clinical course and management
Based on the clinical, serological, and histopathological findings, a diagnosis of juvenile systemic
sclerosis, localized form with risk of systemic progression, was established. The case was discussed
with pediatric rheumatology, and treatment with oral methotrexate at 10 mg/m²/week was initiated,
along with folic acid supplementation and photoprotection measures. Multidisciplinary follow-up was
recommended, including periodic cardiopulmonary evaluations for early detection of complications.
Laboratory studies
Initial laboratory tests revealed the following:
Immunologic profile:
● Complete blood count: hemoglobin
12.4 g/dL, leukocytes 6,500/μL, platelets
280,000/μL.
● Serum chemistry: glucose 88 mg/dL,
urea 28 mg/dL, creatinine 0.5 mg/dL.
● Liver function tests: AST 25 U/L, ALT
21 U/L, ALP 180 U/L.
● Erythrocyte sedimentation rate: 36
mm/h.
● C-reactive protein: 1.2 mg/dL.
● ANA positive, speckled pattern, at a titer
of 1:320.
● Anti–topoisomerase I (Scl-70)
antibodies positive.
● Anti-centromere antibodies negative.
● Anti-Smith and anti-RNP antibodies
negative.
● Rheumatoid factor and anti-CCP
antibodies negative.
● Complement C3 and C4 within normal
ranges.
pág. 9809
At the 6-month follow-up, the patient demonstrated stabilization of the cutaneous lesion, with no
development of new plaques or systemic involvement.
Discussion
Systemic sclerosis (SSc) is a heterogeneous disease with a clinical spectrum that differs widely between
adult and pediatric populations. In children, the most frequent form is localized scleroderma (morphea),
while the systemic variant accounts for less than 5% of cases, with onset usually occurring during
adolescence6,7. Presentation at preschool age, as in this case, is exceedingly rare and has only been
reported sporadically in the literature12,13.
Characteristic Adults Pediatric
Age of onset Peak between 30–50 years1,2 <16 years in <5% of cases6,7
Predominant sex Female-to-male ratio 3–6:12,3
Female predominance also
observed, but with a lower ratio
(≈2:1)7
Most frequent clinical form
Systemic, either diffuse or limited
(CREST)1,2
Localized (morphea) much more
common; systemic form very
rare6,8
Initial cutaneous
manifestations
Raynaud’s phenomenon, distal skin
thickening, telangiectasias2,4
Indurated plaques, linear or
localized morphea; Raynaud’s
phenomenon less frequent7–9
Associated autoantibodies
ANA >90%, anti-centromere
(limited), anti–Scl-70 (diffuse)2,4
ANA frequent, but specific
autoantibodies less consistent;
Scl-70 may be positive in some
juvenile systemic cases7,9
Visceral involvement
Pulmonary (interstitial fibrosis),
pulmonary hypertension,
gastrointestinal, renal, cardiac2,5
Less frequent at onset; risk of
pulmonary and cardiac
involvement increases during
At the 6-month follow-up, the patient demonstrated stabilization of the cutaneous lesion, with no
development of new plaques or systemic involvement.
Discussion
Systemic sclerosis (SSc) is a heterogeneous disease with a clinical spectrum that differs widely between
adult and pediatric populations. In children, the most frequent form is localized scleroderma (morphea),
while the systemic variant accounts for less than 5% of cases, with onset usually occurring during
adolescence6,7. Presentation at preschool age, as in this case, is exceedingly rare and has only been
reported sporadically in the literature12,13.
Characteristic Adults Pediatric
Age of onset Peak between 30–50 years1,2 <16 years in <5% of cases6,7
Predominant sex Female-to-male ratio 3–6:12,3
Female predominance also
observed, but with a lower ratio
(≈2:1)7
Most frequent clinical form
Systemic, either diffuse or limited
(CREST)1,2
Localized (morphea) much more
common; systemic form very
rare6,8
Initial cutaneous
manifestations
Raynaud’s phenomenon, distal skin
thickening, telangiectasias2,4
Indurated plaques, linear or
localized morphea; Raynaud’s
phenomenon less frequent7–9
Associated autoantibodies
ANA >90%, anti-centromere
(limited), anti–Scl-70 (diffuse)2,4
ANA frequent, but specific
autoantibodies less consistent;
Scl-70 may be positive in some
juvenile systemic cases7,9
Visceral involvement
Pulmonary (interstitial fibrosis),
pulmonary hypertension,
gastrointestinal, renal, cardiac2,5
Less frequent at onset; risk of
pulmonary and cardiac
involvement increases during
pág. 9810
adolescence6,7,9
Prognosis
Mortality 5–8 times higher than the
general population; main causes:
pulmonary hypertension and
pulmonary fibrosis10,11
Overall better prognosis, but
systemic cases may progress with
severe complications7,9
Standard treatment
Immunosuppressants
(methotrexate, mycophenolate,
cyclophosphamide), vasodilators,
antifibrotic agents2,5
Similar to adults, adjusted to age
and tolerance; methotrexate most
commonly used as first-line in
juvenile forms8,9
Early diagnosis in pediatric patients is challenging due to clinical overlap with other indurated
dermatoses and the lack of validated diagnostic criteria specifically for children. Nevertheless, positivity
for ANA and anti–topoisomerase I (Scl-70), along with compatible histopathological findings, provide
strong evidence to support the clinical suspicion and differentiate it from other entities such as localized
morphea or cutaneous lupus erythematosus3,8,14.
Nailfold capillaroscopy, as performed in our patient, is a non-invasive tool that allows the detection of
early microvascular alterations and is highly useful for identifying patients at risk of progression to
systemic involvement15. Recent studies confirm that typical SSc capillaroscopic patterns can be present
from the earliest phases of the disease, even in childhood16.
With respect to systemic assessment, it is recommended to rule out visceral involvement from the outset,
particularly pulmonary and cardiac. In this case, high-resolution chest CT and pulmonary function tests
were normal, and echocardiography showed no evidence of pulmonary hypertension. These findings are
consistent with pediatric cohorts, where initial visceral involvement is uncommon, but its incidence
increases over time, justifying close follow-up7,9,17.
Immunosuppressive therapy remains the cornerstone of management. Methotrexate is considered first-
line treatment for progressive cutaneous forms or localized disease at risk of systemic involvement in
children, with documented efficacy in several studies and an acceptable safety profile18,19. In refractory
adolescence6,7,9
Prognosis
Mortality 5–8 times higher than the
general population; main causes:
pulmonary hypertension and
pulmonary fibrosis10,11
Overall better prognosis, but
systemic cases may progress with
severe complications7,9
Standard treatment
Immunosuppressants
(methotrexate, mycophenolate,
cyclophosphamide), vasodilators,
antifibrotic agents2,5
Similar to adults, adjusted to age
and tolerance; methotrexate most
commonly used as first-line in
juvenile forms8,9
Early diagnosis in pediatric patients is challenging due to clinical overlap with other indurated
dermatoses and the lack of validated diagnostic criteria specifically for children. Nevertheless, positivity
for ANA and anti–topoisomerase I (Scl-70), along with compatible histopathological findings, provide
strong evidence to support the clinical suspicion and differentiate it from other entities such as localized
morphea or cutaneous lupus erythematosus3,8,14.
Nailfold capillaroscopy, as performed in our patient, is a non-invasive tool that allows the detection of
early microvascular alterations and is highly useful for identifying patients at risk of progression to
systemic involvement15. Recent studies confirm that typical SSc capillaroscopic patterns can be present
from the earliest phases of the disease, even in childhood16.
With respect to systemic assessment, it is recommended to rule out visceral involvement from the outset,
particularly pulmonary and cardiac. In this case, high-resolution chest CT and pulmonary function tests
were normal, and echocardiography showed no evidence of pulmonary hypertension. These findings are
consistent with pediatric cohorts, where initial visceral involvement is uncommon, but its incidence
increases over time, justifying close follow-up7,9,17.
Immunosuppressive therapy remains the cornerstone of management. Methotrexate is considered first-
line treatment for progressive cutaneous forms or localized disease at risk of systemic involvement in
children, with documented efficacy in several studies and an acceptable safety profile18,19. In refractory
pág. 9811
cases, mycophenolate mofetil, cyclophosphamide, or biologic agents such as tocilizumab have been
used, although evidence in children is limited and largely extrapolated from adult experience20,21.
The prognosis in pediatric patients is generally more favorable than in adults, especially when there is
no initial visceral involvement. Nonetheless, mortality associated with cardiopulmonary complications
remains significant, underscoring the importance of multidisciplinary follow-up involving pediatric
rheumatology, dermatology, and pulmonology10,11,21.
Finally, this case contributes to the literature by documenting a rare presentation of systemic sclerosis
in preschool age, reinforcing the need for comprehensive management and the creation of international
pediatric registries to improve understanding of the disease in this population21.
CONCLUSIONS
Systemic sclerosis in childhood is an uncommon condition, and its presentation at preschool age is
exceptional. This case highlights the importance of considering the disease in the differential diagnosis
of indurated dermatoses in children, particularly when accompanied by positive autoantibodies and
compatible histopathological findings.
A multidisciplinary approach, including dermatology, rheumatology, and pediatric pulmonology, is
essential for the early detection of potentially severe systemic complications. Nailfold capillaroscopy
and systemic screening studies allow for close monitoring and timely management.
Immunomodulatory treatment with methotrexate represents the first-line therapy in this age group and
may stabilize cutaneous disease, although long-term follow-up is required due to the risk of progressive
cardiopulmonary involvement.
Finally, this case expands the existing literature on juvenile systemic sclerosis, underscoring the need
for international multicenter registries to better understand the clinical course, prognostic factors, and
optimal therapeutic strategies in the pediatric population
REFERENCIAS BIBLIOGRÁFICAS
Castañeda NG, Rubio ER, Emperiale V, Hajkhan AM. Esclerosis sistémica. Medicine (Madrid).
2021;13(31):1769–78. doi:10.1016/j.med.2021.04.004
Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685–99. doi:10.1016/S0140-
6736(17)30933-9
cases, mycophenolate mofetil, cyclophosphamide, or biologic agents such as tocilizumab have been
used, although evidence in children is limited and largely extrapolated from adult experience20,21.
The prognosis in pediatric patients is generally more favorable than in adults, especially when there is
no initial visceral involvement. Nonetheless, mortality associated with cardiopulmonary complications
remains significant, underscoring the importance of multidisciplinary follow-up involving pediatric
rheumatology, dermatology, and pulmonology10,11,21.
Finally, this case contributes to the literature by documenting a rare presentation of systemic sclerosis
in preschool age, reinforcing the need for comprehensive management and the creation of international
pediatric registries to improve understanding of the disease in this population21.
CONCLUSIONS
Systemic sclerosis in childhood is an uncommon condition, and its presentation at preschool age is
exceptional. This case highlights the importance of considering the disease in the differential diagnosis
of indurated dermatoses in children, particularly when accompanied by positive autoantibodies and
compatible histopathological findings.
A multidisciplinary approach, including dermatology, rheumatology, and pediatric pulmonology, is
essential for the early detection of potentially severe systemic complications. Nailfold capillaroscopy
and systemic screening studies allow for close monitoring and timely management.
Immunomodulatory treatment with methotrexate represents the first-line therapy in this age group and
may stabilize cutaneous disease, although long-term follow-up is required due to the risk of progressive
cardiopulmonary involvement.
Finally, this case expands the existing literature on juvenile systemic sclerosis, underscoring the need
for international multicenter registries to better understand the clinical course, prognostic factors, and
optimal therapeutic strategies in the pediatric population
REFERENCIAS BIBLIOGRÁFICAS
Castañeda NG, Rubio ER, Emperiale V, Hajkhan AM. Esclerosis sistémica. Medicine (Madrid).
2021;13(31):1769–78. doi:10.1016/j.med.2021.04.004
Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390(10103):1685–99. doi:10.1016/S0140-
6736(17)30933-9
pág. 9812
Varga J, Trojanowska M, Kuwana M. Pathogenesis of systemic sclerosis: recent insights of
molecular and cellular mechanisms and therapeutic opportunities. J Scleroderma Relat Disord.
2017;2(3):137–52. doi:10.5301/jsrd.5000249
Rodríguez-Pintó I, Simeón-Aznar CP, et al. Epidemiology of systemic sclerosis: a systematic review of
the literature. Clin Epidemiol. 2016;8:61–72. doi:10.2147/CLEP.S99680
Elhai M, Avouac J, Allanore Y. Systemic sclerosis in adults and children: clinical manifestations and
diagnosis. Rheumatology (Oxford). 2020;59(Suppl 5):v19–29.
doi:10.1093/rheumatology/keaa573
Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood
using administrative claims data from the United States. Journal of Scleroderma and Related
Disorders. 2018;3(2):189–190. doi:10.1177/2397198318763701
Martini G, Foeldvari I, Russo R, et al. Systemic sclerosis in childhood: clinical and immunologic
features of 153 patients in an international database. Arthritis Rheum. 2006;54(12):3971–8.
doi:10.1002/art.22179
Tan HC, Poh CK, Cai Y, Wang W. Anti-fibrosis effect of BMP-7 peptide functionalization on cobalt
chromium alloy. J Orthop Res. 2013 Jun;31(6):983-90. doi:10.1002/jor.22313.
PMID:23456668.
Foeldvari I, Torok KS. Review for best practice in clinical rheumatology juvenile systemic sclerosis –
Updates and practice points. Best Pract Res Clin Rheumatol. 2021;35(3):101688.
doi:10.1016/j.berh.2021.101688. PMID:33896752.
Allanore Y, Simms R, Distler O, et al. Systemic sclerosis. Nat Rev Dis Primers. 2015;1:15002.
doi:10.1038/nrdp.2015.2
Elhai M, Meune C, Boubaya M, et al. Mapping and predicting mortality from systemic sclerosis. Ann
Rheum Dis. 2017;76(11):1897–905. doi:10.1136/annrheumdis-2017-211448
Zulian F, Woo P, Athreya BH, et al. The Pediatric Rheumatology European Society/American College
of Rheumatology/European League Against Rheumatism classification criteria for juvenile
systemic sclerosis. Arthritis Rheum. 2007;57(2):203–12. doi:10.1002/art.22551
Varga J, Trojanowska M, Kuwana M. Pathogenesis of systemic sclerosis: recent insights of
molecular and cellular mechanisms and therapeutic opportunities. J Scleroderma Relat Disord.
2017;2(3):137–52. doi:10.5301/jsrd.5000249
Rodríguez-Pintó I, Simeón-Aznar CP, et al. Epidemiology of systemic sclerosis: a systematic review of
the literature. Clin Epidemiol. 2016;8:61–72. doi:10.2147/CLEP.S99680
Elhai M, Avouac J, Allanore Y. Systemic sclerosis in adults and children: clinical manifestations and
diagnosis. Rheumatology (Oxford). 2020;59(Suppl 5):v19–29.
doi:10.1093/rheumatology/keaa573
Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood
using administrative claims data from the United States. Journal of Scleroderma and Related
Disorders. 2018;3(2):189–190. doi:10.1177/2397198318763701
Martini G, Foeldvari I, Russo R, et al. Systemic sclerosis in childhood: clinical and immunologic
features of 153 patients in an international database. Arthritis Rheum. 2006;54(12):3971–8.
doi:10.1002/art.22179
Tan HC, Poh CK, Cai Y, Wang W. Anti-fibrosis effect of BMP-7 peptide functionalization on cobalt
chromium alloy. J Orthop Res. 2013 Jun;31(6):983-90. doi:10.1002/jor.22313.
PMID:23456668.
Foeldvari I, Torok KS. Review for best practice in clinical rheumatology juvenile systemic sclerosis –
Updates and practice points. Best Pract Res Clin Rheumatol. 2021;35(3):101688.
doi:10.1016/j.berh.2021.101688. PMID:33896752.
Allanore Y, Simms R, Distler O, et al. Systemic sclerosis. Nat Rev Dis Primers. 2015;1:15002.
doi:10.1038/nrdp.2015.2
Elhai M, Meune C, Boubaya M, et al. Mapping and predicting mortality from systemic sclerosis. Ann
Rheum Dis. 2017;76(11):1897–905. doi:10.1136/annrheumdis-2017-211448
Zulian F, Woo P, Athreya BH, et al. The Pediatric Rheumatology European Society/American College
of Rheumatology/European League Against Rheumatism classification criteria for juvenile
systemic sclerosis. Arthritis Rheum. 2007;57(2):203–12. doi:10.1002/art.22551
pág. 9813
Zulian F, Vallongo C, Woo P, et al. Localized scleroderma in childhood is not just a skin disease.
Arthritis Rheum. 2005;52(9):2873–81. doi:10.1002/art.21265
Li SC, Torok KS, Pope E, et al. Development of consensus treatment plans for juvenile localized
scleroderma. Arthritis Care Res (Hoboken). 2012;64(8):1175–85. doi:10.1002/acr.21677
Cutolo M, Sulli A, Smith V. Assessing microvascular changes in systemic sclerosis diagnosis and
management. Nat Rev Rheumatol. 2010;6(10):578–587. doi:10.1038/nrrheum.2010.104
Herrick AL, Ennis H, Bhushan M, et al. Nailfold capillaroscopy in children with connective tissue
disease: a prospective multicentre study. Arthritis Care & Research (Hoboken).
2013;65(9):1423–1431. doi:10.1002/acr.22007.
Zulian F, Cuffaro G, Sperotto F. Methotrexate in juvenile localized scleroderma: state of the art.
Clinical and Experimental Rheumatology. 2015;33(4 Suppl 91):S109–S112. PMID:26314405.
Pope JE, Denton CP. State-of-the-art evidence in the treatment of systemic sclerosis. Nat Rev
Rheumatol. 2023;19(4):212–226. doi:10.1038/s41584-023-00909-5.
Foeldvari I, Constantin T, Zulian F, et al. Tocilizumab in juvenile systemic sclerosis: first report from
the international juvenile scleroderma cohort. Rheumatology (Oxford). 2020;59(2):435–439.
doi:10.1093/rheumatology/kez310.
Foeldvari I, Martini G, Russo R, Cuttica R, Pilkington C, Katsicas MM, et al. Survival and disease
progression in juvenile systemic sclerosis: a multinational, multicenter cohort study. Arthritis
& Rheumatology. 2020;72(11):1915–1924. doi:10.1002/art.41449.
Foeldvari I, Wulffraat N, Kasapcopur O, et al. The Juvenile Systemic Sclerosis Inception Cohort (jSSc):
an international inception cohort study. Pediatr Rheumatol Online J. 2019;17(1):85.
doi:10.1186/s12969-019-0390-5
Zulian F, Vallongo C, Woo P, et al. Localized scleroderma in childhood is not just a skin disease.
Arthritis Rheum. 2005;52(9):2873–81. doi:10.1002/art.21265
Li SC, Torok KS, Pope E, et al. Development of consensus treatment plans for juvenile localized
scleroderma. Arthritis Care Res (Hoboken). 2012;64(8):1175–85. doi:10.1002/acr.21677
Cutolo M, Sulli A, Smith V. Assessing microvascular changes in systemic sclerosis diagnosis and
management. Nat Rev Rheumatol. 2010;6(10):578–587. doi:10.1038/nrrheum.2010.104
Herrick AL, Ennis H, Bhushan M, et al. Nailfold capillaroscopy in children with connective tissue
disease: a prospective multicentre study. Arthritis Care & Research (Hoboken).
2013;65(9):1423–1431. doi:10.1002/acr.22007.
Zulian F, Cuffaro G, Sperotto F. Methotrexate in juvenile localized scleroderma: state of the art.
Clinical and Experimental Rheumatology. 2015;33(4 Suppl 91):S109–S112. PMID:26314405.
Pope JE, Denton CP. State-of-the-art evidence in the treatment of systemic sclerosis. Nat Rev
Rheumatol. 2023;19(4):212–226. doi:10.1038/s41584-023-00909-5.
Foeldvari I, Constantin T, Zulian F, et al. Tocilizumab in juvenile systemic sclerosis: first report from
the international juvenile scleroderma cohort. Rheumatology (Oxford). 2020;59(2):435–439.
doi:10.1093/rheumatology/kez310.
Foeldvari I, Martini G, Russo R, Cuttica R, Pilkington C, Katsicas MM, et al. Survival and disease
progression in juvenile systemic sclerosis: a multinational, multicenter cohort study. Arthritis
& Rheumatology. 2020;72(11):1915–1924. doi:10.1002/art.41449.
Foeldvari I, Wulffraat N, Kasapcopur O, et al. The Juvenile Systemic Sclerosis Inception Cohort (jSSc):
an international inception cohort study. Pediatr Rheumatol Online J. 2019;17(1):85.
doi:10.1186/s12969-019-0390-5