Scleroderma is a rheumatic disease that affects both children and adults, with the estimated annual incidence rate of 1.4–5.6 per 100.000 in adults, and 1–3 per 100.000 children(1,2). Juvenile scleroderma (JS) is a rare, chronic disease with an autoimmune background that affects the connective tissue by excessive collagen production(3). Girls are nearly 4 times more frequently affected than boys(4). There are two main types of JS: juvenile localized scleroderma (jLS) and juvenile systemic scleroderma (jSSc), which differ in clinical presentation, but share same pathophysiology including the inflammatory phase associated with endothelial dysfunction(5). The two main types are further divided into more subtypes based on additional clinical findings (Tab. 1). There is a noticeable discrepancy in incidence between jLS and jSSc which is estimated up to be 2.7 cases per 100,000 per year in jLS, and 0.27 per 1,000,000 per year in jSSc. This is contrary to the adult population, where systemic scleroderma (SSc) is more frequent than localized scleroderma (LS)(2). Arthritis and myositis, which can occur during the course of the disease, are also more frequent in children. Raynaud’s phenomenon and skin sclerosis may also be observed(4). Racial predilection is evident in jLS, with up to 82% of children affected being Caucasians. JSSc does not follow this pattern(3).
Juvenile systemic scleroderma | Juvenile localized scleroderma |
---|---|
Juvenile systemic sclerosis | Morphea |
Diffuse cutaneous (dcSsc) | Plaque morphea |
Limited cutaneous (lcSsc) | Keloidal morphea |
Generalized morphea | |
Bullous morphea | |
Skin limited systemic sclerosis | Linear scleroderma |
(CREST syndrome) | Linear morphea |
En coup de sabre | |
Parry-Romberg syndrome - hemifacial atrophy | |
Overlap syndrome | Eosinophilic fasciitis |
The diagnosis of jLS remains challenging. It is diagnosed by a rheumatologist or dermatologist based on the patient’s history and physical examination. Clinical assessment of skin involvement is based on the modified Rodnan score. Multiple skin folds are assessed on a scale from 0 to 3, with 3 standing for immobile, rock-hard skin thickening(3). A skin biopsy may also be done to confirm the diagnosis. There are no specific laboratory tests with diagnostic utility. RF and autoantibody profiles are performed mainly to exclude other autoimmune diseases. Up to 50% of patients may present with elevated levels of ANA, AHA, and anti-ssDNA(6).
Imaging, although commonly used, is still not included in any diagnostic criteria and constitutes only an auxiliary tool. In this article, we aim to review the imaging techniques available for juvenile scleroderma including classic radiography (CR), ultrasonography (US), and magnetic resonance imaging (MRI). Computed tomography (CT), which requires a high dose of radiation, is rarely used in children. We will focus on each type of scleroderma separately, and describe imaging findings that can be seen in children affected.
JLS is the most frequent subtype of scleroderma in children. Excessive collagen production leads to thickening and hardening of limited areas of the skin and subdermal tissues. The manifestation of the disease ranges from very small superficial plaques involving only the skin to extensive lesions causing significant functional and esthetic deformity due to bone undergrowth secondary to skin fibrotic changes following active inflammation (Fig. 1)(8). Extracutaneous involvement can also occur, with the musculoskeletal system (MSK) being the most commonly affected(3). It is important to take that fact into account, as Adrovic
JLS presents in various patterns of skin involvement, and includes several subtypes classified by the size and localization of skin changes (Tab. 1). The most common is linear scleroderma, followed by plaque and generalized morphea. Other subtypes, such as deep and bullous morphea, are very rare(8).
There are a number of pathologies that occur in jLS and can be observed in ultrasonography, MRI or classic radiography.
When examining the skin or other superficial structures by ultrasound, high-frequency transducers must be used. Thickening and hypervascularization may be found in B-mode and Doppler studies of the cutis and subcutaneous tissue (Fig. 1). In 2009, Li
Tenosynovitis and skin atrophic changes may lead to flexion contractures which are most characteristic in the metacarpophalangeal (MCP) and interphalangeal (IP) joints(13). As this can result in disability, monitoring affected joints by US seems to be very beneficial.
Finally, soft tissue calcifications, which are typical in scleroderma, are by far best seen on radiographs or CT. However, the Doppler modality also enables visualization of those small calcifications, as the twinkling artifact is present (Fig. 2). It is a phenomenon observed on color and power Doppler examination right behind stationary echogenic surfaces. It detects minute calcific deposits before their size is capable of eliciting an acoustic shadow. It is worth bearing in mind, though, that this artifact can mimic blood flow or inflammation(14). Modern MicroPure option can be useful in detecting clustered microcalcifications that are not seen in B-mode imaging(15). This modality is also useful in ruling out the presence of calcifications.
Radiography may visualize several types of lesions in jLS. Bone resorption of the distal phalanges (acroosteolysis) is the most specific one. As mentioned before, soft tissue calcifications such as calcinosis cutis and subcutaneous calcification are also frequently seen and very well visualized (Fig. 3). Contractures and subluxations seen on CR are results of tendons, fascia and bursal fibrosis. Joint space narrowing, erosions, or bone atrophy are very rare signs(16). In the study mentioned before performed by Osimina
MRI can show abnormalities of the skin, and subcutaneous and deep tissues. It is a modality of choice and gold standard in many musculoskeletal entities. Thanks to the lack of ionizing radiation and high soft tissue contrast MRI is a valuable tool in the diagnosis of juvenile scleroderma, however long acquisition time and the necessity of sedation in younger children are among the disadvantages of this option. Examination of specific anatomical regions or whole-body MRI may be performed. Inflammatory infiltration and atrophy of subcutaneous fat are the most common MRI findings in jLS(15). In linear scleroderma “en coup de sabre”, in addition to band-like sclerotic lesions typically involving the fronto-parietal regions of the scalp, children often present with neurologic symptoms. Muscle inflammation (Fig. 4), fascial involvement and bone marrow edema are less frequent, but can be found in MRI images in jLS, the last is exclusively seen on MRI. MRI may especially be needed in the overlapping syndromes, which most commonly concern scleroderma and dermatomyositis (scleromyositis); MRI is the imaging modality of choice for the latter (Fig. 4).
JSSc is extremely rare in children. It is associated with fibrous changes in internal organs which can lead to pulmonary, cardiovascular, gastrointestinal, renal, neurological, musculoskeletal and ocular complications. Therefore, this type of scleroderma has a poorer prognosis(17).
Just like in jLS, the skin and musculoskeletal system are the most frequently affected in JS. However, the main prognostic factor in this disorder is the involvement of the cardiopulmonary system. In this scenario, interstitial lung disease may develop, leading to pulmonary hypertension, and ultimately resulting in heart failure. Pulmonary fibrosis is considered to be the main cause of mortality in adults, while cardiac failure is the leading cause of death in the juvenile population(18).
Some of the major clinical manifestations are Raynaud’s phenomenon (RP) and skin changes affecting the hands. RP is a vasospasm of the peripheral arteries and arterioles which leads to a triphasic color change of the hands: first pallor, then blue, and at the end red with swelling and pain. RP is quite common in jSSc and according to Scalpina
Internal organ involvement in children is not as common as in adults. According to Scalpina
Compared to the adult onset, MSK involvement is more common in juvenile SSc. The most prevalent manifestations are arthralgia, arthritis and myalgia. Approximately 25% to 40% children experience arthritis(1). Foeldavi
Similarly to jLS, high-frequency ultrasonography can be used to evaluate and monitor skin thickness and echogenicity. In the case of jSSc, skin thickness was associated with greater disease severity, and was shown to predict the extent of visceral involvement, and patient prognosis and survival. Likewise jLS, excessive collagen production and subsequent fibrosis of the skin lead to increased skin stiffness which nowadays can be measured during ultrasound examination using shear wave elastography. Stiffness is coded in appropriate colors in the elastography box which is usually superimposed on B-mode gray-scale presentation. A very high sensitivity, specificity and reliability of shear wave elastography in the assessment of SSc skin involvement was confirmed in a study by Yang
Radiographs in jSSc may show bone resorption of the distal phalanges (acroosteolysis) with periarticular calcification and atrophy at the tips of the fingers. Bone loss and subcutaneous calcification are additional findings that might be seen. Resorption of the first carpometacarpal joint (CMC) with radial subluxation is a characteristic feature on radiographs of the hands. Shortening of long bones is possible due to soft tissues fibrosis. Dilatation of the esophagus in the most typical sign, along with gastro-esophageal reflux due to reduced sphincter tone(16).
MRI, as far as systemic sclerosis is concerned, plays an important role in the diagnosis of brain abnormalities which are, fortunately, extremely rare. Brain calcifications and hyperintense white matter signals can be seen on MRI(17). It is also useful as an additional diagnostic tool when internal organ involvement is suspected.
CT is rarely performed in children, as it requires a high dose of radiation. It is, however, the main tool for the assessment of interstitial lung disease which is the main cause of mortality in children with jSSc.
Juvenile scleroderma is a chronic disease with no cure. The treatment focuses on the management of inflammation of specific organs affected. Juvenile localized scleroderma, despite having a much better prognosis than juvenile systemic scleroderma, with almost no mortality, has a poorer prognosis when diagnosed in childhood. Due to the fact that the condition affects children during their intensive growth period, it may cause significant functional deformities such as extremity length differences, joint contractions, and growth retardation. This is why a quick diagnosis and appropriate treatment at the early stage of jLS are crucial. Imaging, especially new high-frequency ultrasonography, shear-wave sonoelastography, and MRI, may provide early diagnosis and good monitoring of the disease. They are essential tools for the treatment because immunosuppressive therapy is effective only in the active, but not the sclerotic phase of the disease. Due to a limited population of patients, studies of juvenile scleroderma are very few and insufficient. Imaging techniques, as well as the quality and protocols of imaging, vary across different centers. Further research needs to be done to standardize those protocols. In addition, scleroderma belonging to the group of diffuse rheumatoid connective tissue disorders, may occur with another disease simultaneously, creating what is called an overlap syndrome – a term used to define the coexistence of more than one connective tissue condition. Precise diagnosis in these cases is very demanding, especially in children(25). Since imaging techniques are constantly being developed, the implementation of new technologies, software and protocols may help in the diagnosis, monitoring and treatment of rare systemic diseases such as juvenile scleroderma. This is a crucial aspect, as treatment decisions and prognostic assessment are directly related to imaging results along with clinical findings.