Juvenile Localized Scleroderma


Type

Subtype

Features

1. Circumscribed morphea

(a) Superficial

Oval or round circumscribed areas of induration limited to the epidermis and dermis, often with altered pigmentation and violaceous, erythematous halo (lilac ring)

They can be single or multiple

(b) Deep

Oval or round circumscribed deep induration of the skin involving the subcutaneous tissue extending to the fascia and underlying muscle. The lesions can be single or multiple

Sometimes the primary site of involvement is in the subcutaneous tissue without involvement of the skin

2. Linear scleroderma

(a) Trunk/limbs

Linear induration involving the dermis, subcutaneous tissue and, sometimes, muscle and underlying bone and affecting the limbs and/or the trunk

(b) Head

En coup de sabre (ECDS). Linear induration of the skin that affects the face and/or the scalp and sometimes involves the muscle and underlying bone

Parry-Romberg or progressive hemifacial atrophy loss of tissue on one side of the face that may involve the dermis, subcutaneous tissue, muscle and bone. The skin is unaffected and mobile

3. Generalized morphea
 
Induration of the skin starting as individual plaques (4 or more and larger than 3 cm) that become confluent and involve at least two anatomic sites

4. Pansclerotic morphea
 
Circumferential involvement of the limb(s) affecting the skin, subcutaneous tissue, muscle and bone. The lesion may also involve other areas of the body without internal organs involvement

5. Mixed morphea
 
Combination of two or more of the previous subtypes. The order of the concomitant subtypes, specified in brackets, will follow their predominant representation in the individual patient [i.e. mixed (linear circumscribed)]





Epidemiology


Although JLS is relatively uncommon, it is far more common than systemic sclerosis in childhood, by a ratio of at least 10:1 [4]. There is a mild female predilection with the F/M ratio 2.4:1 [2]. The mean age at disease onset is 7.3 years, and a few cases with onset at birth, the so-called congenital localized scleroderma, have been also described [5].


Clinical Manifestations


Circumscribed morphea (CM) is characterized by oval or round circumscribed areas of induration surrounded by a violaceous halo (Fig. 29.1). It is confined to the dermis with only occasional involvement of the superficial panniculus.

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Fig. 29.1
Circumscribed morphea of the lower left eyelid, characterized by an area of induration with waxy consistence and ivory colour, surrounded by an inflammatory edge

When there are four or more plaques with individual plaques that are larger than 3 cm and they become confluent involving at least two out of seven anatomic sites (head-neck, right upper extremity, left upper extremity, right lower extremity, left lower extremity, anterior trunk, posterior trunk), it is called generalized morphea (GM) (Fig. 29.2). Unilateral GM has been proposed as an uncommon variant, usually beginning in childhood [1].

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Fig. 29.2
Generalized morphea involving, symmetrically, the upper trunk in a 10-year-old boy. Note the bluish halo of some lesions, named lilac ring

Linear scleroderma, the most common subtype in children and adolescents, is characterized by one or more linear streaks that can extend through the dermis, subcutaneous tissue and muscle to the underlying bone, causing significant deformities (Fig. 29.3). The upper or lower extremities can be affected but also the face or scalp, as in the en coup de sabre variety (ECDS). The Parry-Romberg syndrome (PRS), characterized by hemifacial atrophy of the skin and tissue below the forehead, with mild or absent involvement of the superficial skin is considered the severe end of the spectrum of ECDS and for this reason is included in the subtype of linear scleroderma [6]. Evidence for this close relationship is the presence of associated disorders, including seizures, central nervous system (CNS) abnormalities and dental and ocular abnormalities, reported with similar prevalence in both conditions [79].

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Fig. 29.3
Linear scleroderma in active phase of the right upper limb involving the fourth and the fifth fingers with flexion contracture of the fourth proximal interphalangeal joint

Pansclerotic morphea, an extremely rare but severe subtype, is characterized by generalized full-thickness involvement of the skin of the trunk, extremities, face and scalp with sparing of the fingertips and toes. It is more common in children than adults. Recent reports raised the attention of the possible evolution of chronic ulcers, frequently complicating pansclerotic morphea, to squamous cell carcinoma, a threatening complication already reported in LS [1012].

Conversely to what has been reported for many years, JLS is not exclusively confined to the skin but can have many extra-cutaneous features. A recent multinational study reported that almost one fourth of the patients present extra-cutaneous manifestations [13]. The overall distribution of these manifestations includes arthritis 19 %, neurological findings 4 %, associated autoimmune conditions 3 %, vascular changes (i.e. Raynaud’s phenomenon, deep vein thrombosis) 2 % and ocular or gastrointestinal abnormalities in 2 %.

Articular involvement is the most frequent finding, especially in linear scleroderma. Children who develop arthritis often have a positive rheumatoid factor (RF) and sometimes an elevated erythrocyte sedimentation rate (ESR) and circulating autoantibodies [13]. The most frequent neurological conditions are seizures and headaches, although behavioural changes and learning disabilities have been also described [13, 14]. Abnormalities on magnetic resonance imaging (MRI), such as calcifications, white matter changes, vascular malformations and vasculitis, also have been reported [1517]. Although most of the imaging abnormalities are non-specific, biopsies have shown sclerosis, fibrosis, gliosis as well as vasculitis [17].

Gastro-oesophageal reflux (GER) is the only gastrointestinal complication reported so far in JLS [2, 18, 19].


Differential Diagnosis


JLS should be differentiated from systemic disease. In the most common form, linear scleroderma, the lesions are discrete, limited to a single extremity and easily differentiated from juvenile systemic sclerosis (JSSc). The more difficult diagnostic challenge is to differentiate JSSc from the diffuse and deep forms of localized scleroderma, such as pansclerotic morphoea. These patients, in contrast to those with JSSc, rarely have Raynaud’s phenomenon and do not develop symptomatic evidence of internal organ involvement. Occasionally, the deep forms of JLS may be confused with juvenile idiopathic arthritis in that they can manifest with contractures of the hands, arthralgias and sometimes synovitis and may have a positive RF test result. In cases such as these, further testing may document the presence of anti-histone antibodies, hypergammaglobulinaemia and eosinophilia typical of the deep varieties of LS.


Autoantibodies


Antinuclear antibodies (ANA) are present in more than 40 % of patients with JLS [2]. This frequency is lower than in adult with LS [20] but is higher than seen in the normal population. In children, there is no correlation between the presence of ANA and a particular subtype or disease course [2]. Of interest, anti-topoisomerase I antibodies (anti-Scl-70), a marker of SSC in adults, were found to be positive in 2–3 % of children with JLS but not in adults with LS [2, 20]. Conversely, anti-centromere antibodies (ACA) were found in 12 % of adults with LS but only in 1.7 % of children [2, 21]. Whether these antibodies are markers that reflect the immunological component of the disease process or can have a prognostic significance is unclear. It should be noted that none of Scl-70 or ACA-positive patients in a series of 750 JLS patients presented signs or symptoms of internal organ involvement after a mean follow-up of 3.4 years [2].

Rheumatoid factor (RF) has been detected, at low titre, in 16 % of the patients with JLS and significantly correlated with the presence of arthritis [2].

One of the major autoantigens for ANA in JLS is nuclear histone. Anti-histone antibodies (AHA) have been detected in 47 % of patients with JLS with a different prevalence in the various subtypes, higher in GM and lower in circumscribed morphea [20].


Diagnosis and Disease Assessment


The management of JLS is challenging, and the detection of disease activity and progression remains a fundamental problem. Clinical examination is subjective; classical skin scoring methods, utilized in the assessment of systemic sclerosis, cannot be applied. Among the new tools which have been proposed for the assessment of the skin lesions, infrared thermography (IRT), computerized skin score (CSS), ultrasound (US) and magnetic resonance imaging (MRI) are those most frequently used. Infrared thermography (IRT) is able to detect areas of increased temperature caused by the inflammatory process, revealing, in this way, active lesions [22]. This technique has shown to have a very high reproducibility but yields false-positive results in the assessment of old lesions characterized by marked atrophy of the skin and subcutaneous tissues. In these cases, an accurate clinical examination can help differentiate these lesions from the active ones.

The computerized skin score (CSS) consists in the demarcation of hyperemic and indurated borders of the lesions on an adhesive transparent film with different colours [23]. The film, transferred over a cardboard, is scanned and recorded in a computer. Calculation of the affected area is performed by computer software.

Ultrasonography (USG) is another technique that has been proposed for monitoring JLS. USG can detect several abnormalities such as increased blood flow, increased echogenicity due to fibrosis and loss of subcutaneous fat. The first two parameters appear to be signs of active lesions, which disappear in the remission phase. Loss of subcutaneous tissue was found in both active and stable patients [24]. The two main limits of USG are represented by it being an operator-dependent test and the lack of validation as an outcome measure in prospective studies.

MRI is also an important tool in the clinical management of JLS. MRI is clearly most useful when CNS or eye involvement is suspected but is also able to demonstrate the true depth of soft tissue lesions and the degree to which different tissues are involved in other sites [25, 47, 48].

In comparison to USG, MRI has two main disadvantages: the need for sedation in younger patients and the presence of possible artefacts.


Treatment


Over the years, many treatments have been tried for localized scleroderma [26]. Circumscribed morphea generally is of cosmetic concern only, and therefore treatments with potentially significant toxicity are not justified. In general, these lesions will spontaneously remit with residual pigmentation as the only abnormality. Therefore, treatment should be directed mainly at topical therapies such as moisturizing agents, topical glucocorticoids or calcipotriene [27].

Phototherapy with ultraviolet (UV) represents another possible therapeutic choice for localized scleroderma [2833]. Treatment with UVA1 at low, medium and high doses, with or without psoralens (PUVA), all seems to be effective clinically, although high doses seem somewhat better. This approach seems to be much more effective for localized or superficial lesions than for the subtypes with deeper involvement such as linear or generalized scleroderma (Table 29.2) [2833, 4446].


Table 29.2
Phototherapy treatment in localized scleroderma


















































Author (reference)

Treatment

Regimen

No. patients (children)

Follow up

Result

Assessment

Kerscher et al. [28]

UVA1

UVA1 20 J/cm2 for 12 weeks (total number of treatments, 30; cumulative UVA1 dose, 600 J/cm2

20 (0)

12 weeks

Effective (90 %)

Clinical judgement, 20 Mhz USG, histopathology

Kreuter et al. [29]

LdUVA1 + vit D

UVA1 40 sessions in 10 weeks, cumulative dose 800 J\cm2) + calcipotriol ointment 0.005 % twice daily for 10 weeks

19 (19)

10 weeks

Effective (100 %)

Clinical judgement, 20 Mhz USG

Gruss et al. [30]

UVA1

UVA1 20 J/cm2, 4 times/week for 6 weeks, once/week for 6 weeks

3 (0)

12 weeks

Effective (100 %)

Clinical judgement, photos

De Rie et al. [31]

UVA1

UVA1 = 48 J/cm2, 4 times/week for 5 weeks

8 (0)

12 weeks

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Oct 25, 2017 | Posted by in RHEUMATOLOGY | Comments Off on Juvenile Localized Scleroderma
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