Circumscripts of scleroderma (overview) L94.0

Author: Prof. Dr. med. Peter Altmeyer

Co-Autor: Hadrian Tran

All authors of this article

Last updated on: 16.10.2021

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Synonym(s)

circumscribed scleroderma; Circumscripts Scleroderma; CS; Keloid morphea; Linear scleroderma; localized morphea; localized scleroderma; Localized scleroderma; Morphea; Morphea en coup de sabre; Morphea en plaques; Morphoea; scleroderma circumscribed; scleroderma circumscripta; Scleroderma disseminated circumscripts; Scleroderma en coup de sabre; Scleroderma heart-shaped circumscripts; Scleroderma localized; Scleroderma nodular circumscripts; Scleroderma small spotted circumscripts; Scleroderma unilateral circumscripts; ZS

Definition
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Heterogeneous group of chronic, episodic, sclerosing connective tissue diseases of the skin, which, depending on the subtype and localization, have different involvement of skin-related structures such as fatty tissue, muscles, joints and bones. Infection of internal organs such as the heart, lungs, kidneys or gastrointestinal tract is a rarity in circumscribed scleroderma; transitions to systemic scleroderma are just as rare.

The clinical course is generally characterized by an initial livid redness, centrifugal expansion with central pallor, development of sclerosis with surrounding inflammatory rim(lilac ring). It has a considerable clinical spectrum in terms of localization, severity and recurrence rate.

Classification
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Depending on the shape, size and location of the sclerotic hardening of the connective tissue, there are 3 clinical types and various special forms:

Type I Plaque-shaped circumscribed scleroderma (ZS) with variants (about 70% of adults and about 30% of children):

  • Variants:
    • Plaque or morphea type also limited form of CS (about 60% of the total CS)
    • generalized, circumscribed scleroderma (maximum variant of the plaque or morphea type)
    • bullous, circumscribed scleroderma (bullous variant of the plaque type)
    • small spotted, circumscribed scleroderma (Guttata type)
    • unilateral, circumscribed scleroderma
    • Atrophic type ( Atrophodermia idiopathica et progressiva) (about 20% of the total CS collective)

Type II linear (or band-shaped) circumscribed scleroderma (10-30% of adults and about 65% of children):

Type III Profound, circumscribed scleroderma (approx. 12% of children):

An AWF guideline distinguishes between 4 subgroups (limited CS; generalized CS; linear CS, deep CS; as special forms are considered (see above): Pansclerotic disabling disease of children (foudroyant progressive generalized circumscript scleroderma); Hemiatrophia faciei progressiva (type Parry-Romberg); Eosinophilic fasciitis.

Occurrence/Epidemiology
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The incidence is 2/100,000 in the overall population, with analogous incidences reported in children and adolescents. The disease occurs predominantly in whites (85%), in blacks in 5% and in Asians in 3%.

Etiopathogenesis
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  • Unknown. Discussed are genetic (correlation with HLA-B8, DR1, DR5), immunological, autoimmunological, hormonal, viral, toxic, traumatic, drug, neurogenic or vascular factors.
  • In the case of linear CS, in addition to trauma, infections, genetic factors and embryonic disorders, the causes of the development of the disease are suspected to be, among other things, an epigenetic mosaic constellation (see mosaic, cutaneous).
  • Especially in young patients, Borrelia infections can initiate a circumscript scleroderma (Borrelia associated early-onset morphea) or run under the picture of a circumscript scleroderma (Borrelia specific antigens like OspA or OspC have a high antigenic potential and can initiate autoreactive processes). See below Borrelia.
  • Increasingly, the opinion that it is an autoimmunological disease is gaining ground (autoimmunological and rheumatic diseases in the family, accompanying rheumatic or autoimmunological diseases, ANA +).
  • Smad proteins appear to play a role in fibrosis processes at the molecular level. Studies have shown that after UVA1 phototherapy the expression of Smad7 mRNA is decreased in clinically affected areas. Furthermore, antimicrobial peptides and proinflammatory cytokines such as IL-6 and IL-8 seem to play a pathogenetic role. IL-6 mRNA, IL-8 mRNA and ß-defensin mRNA were decreased after UVA1 phototherapy similar to the Smad proteins in clinically affected areas. Further studies are needed to elucidate the pathogenetic relevance with respect to clinical manifestation.

Manifestation
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Manifestation summit: 1st-4th decade of life

Localization
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The trunk (58%), lower extremities (24%), upper extremities (12%) or head (6%) are particularly affected. Changes in the mucous membranes are rarely present. Recess of the perimamillary and genitoanal regions.

Clinical features
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In type I circumscript scleroderma (limited form), different variants are observed:

  • Classical plaque or morphea type: Mostly painless, chronically stationary, localized at the trunk and extremities, varying in size (0.5-30.0 cm or larger), roundish or oval, also widely confluent, centrifugally expanding, sharply defined, white, red or brown flat hardened indurations. In the centre of the indurations there is often the formation of a white or yellow, hard plate caked to the base , in which the follicular structure is missing (destruction of the hair follicles). Often these indurations are surrounded by a ring-shaped, blue-violet to lilac erythema border = Lilac Ring (sign of progression). The lesions of circumscribed scleroderma can be roundish to oval, also structured like a map.
  • Atrophodermia idiopathica et progressiva is a clinical primary atrophying variant of the plaque type with large, little indurated, reddish-brown or red, slightly sunken atrophic areas.
  • The guttata form (also confetti type) of circumscribed scleroderma(Morphea guttata) usually shows disseminated, trunk-accentuated yellowish-white, superficially shiny, little indurated, hardly 1 cm large spots, papules or plaques. Initially, tender red spots can be impressive.
  • According to the AWF guideline, the"generalized form of circumscribed scleroderma" is present when at least three anatomical localizations are affected. Preferably affected are the trunk, thigh and the lumbosacral region. The plaques often occur symmetrically and can conflate into larger areas, then associated with movement disorders. The very rare"disabling pansclerotic morphea", which is a maximum variant of generalized CS, is extremely difficult to progress (see figure). The combination of linear and disseminated large-area areas with only a slight regression tendency of the fibrosis often leads to contractures and wound healing disorders already in childhood.

Type II of circumscript scleroderma (linear or band-shaped circumscript scleroderma):

  • Strip-shaped or band-like or systematized indurations with a longitudinal course (segmental alignment? Blaschko lines?). Location: Found mainly on the extremities (ligamentous circumscript scleroderma) or on the capillitium (often on the forehead: scleroderma en coup de sabre). These can heal as mild forms with hyperpigmentation. More common, however, are rough sclerotic streaks that run across joints and lead to movement restrictions. Linear circumscribed scleroderma of the type "en coup de sabre" is mostly found frontoparietally, mostly paramedically from the eyebrows to the hairy scalp (lesional alopecia). In this case a focal involvement of the CNS can be excluded. A variant of the linear circumscript scleroderma is the so-called progressive facial hemiatrophy(Hemiatrophia faciei progressiva).

Type III of circumscript scleroderma:

  • Deep circumscipt scleroderma(deep morphea) is the rarest subtype of circumscipt scleroderma (<5% of patients). In this case plate-like or nodular indurations can be palpated in the subcutaneous fatty tissue and the adjacent fascia ( sclerofascia, eosinophilic fasciitis). The covering skin can be moved over the induration without being affected. The changes occasionally manifest themselves symmetrically, preferably on the extremities. They may occur in childhood and sometimes manifest themselves without a preceding inflammatory reaction.

In about 20% of cases, extracutaneous manifestations have been observed in a review of adults (s.a. scleroderma, circumscribed juvenile), although these do not play a clinical role (apart from skeletal and muscular changes in the linear forms):

  • skeleton (25-44%): polyarthritis, osteoporosis.
  • Gastrointestinal tract (about 12%): dysphagia, gastroesophageal reflux, diarrhoea, constipation.
  • Genital tract: 38% of patients suffer from lichen sclerosus et atrophicans.
  • Lungs (7%): fibrosis (dyspnea on exertion and at rest), cough, cyanosis.
  • Muscles: myopathy (weakness), pain.
  • Heart: dysrhythmia, cardiac insufficiency, pericardial effusion.
  • Kidney: proteinuria, insufficiency, hypertension.
  • Liver: primary biliary cirrhosis
  • Neurological symptoms: MS (7-10 times higher risk compared to the normal population).

Autoimmunological concomitant diseases: Systemic lupus erythematosus (58 times higher risk than in the normal population); Vitiligo (3.5 times higher risk than in the normal population); Psoriasis vulgaris (1.4-5 times higher risk than in the normal population).

Laboratory
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Antinuclear antibodies are positive (varying according to literature and type) in 7-81% of cases without any indication of systemic involvement. DNA-AK and ENA are negative.

Histology
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  • Inflammatory stage: Dense inflammatory infiltrate, mainly from lymphocytes. Edematous swelling of the collagen fibre bundles. Septal panniculitis in the upper parts of the fatty tissue with spongy or nodular round cell infiltrates at the dermo-subcutaneous border. Rare formation of germinal centres. Enclosure of fat tissue globules by collagenous bundles.
  • Sclerotic stage: wide proliferation of dermal connective tissue at the expense of subcutaneous adipose tissue. Homogenized broadened collagen fibre bundles run parallel to the skin surface. Atrophic adnexes, slit-shaped narrowed vessels. Walled in eccrine sweat glands. Rather sparse perivascular and diffuse lymphocytic infiltrates. Nodular compression of the infiltrates at the border of the subcutis. Broad, homogenized and also edematized fat tissue septums with thinner round cell infiltrates.

Diagnosis
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Characteristic clinical picture. The histological examination is diagnostic but rarely conclusive.

Differential diagnosis
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Early inflammatory phase of limited CS (Morphea) 

  • lichen sclerosus
  • Vitiligo (important differentiation in case of infestation of the genitoanal region; histology is diagnostic in this case)  
  • Erythema chronicum migrans
  • cutane Mastozytose  
  • Granuloma anulare  
  • Bestrahlungsdermatitis  
  • Mycosis fungoides  
  • Drug reactions

Late stage of limited ZS (Morphea) with leading hyperpigmentation.

  • post-inflammatory Hyperpigmentierung  
  • Lichen planus actinicus  
  • Café-au-Lait-Flecken  
  • Erythema dyschromicum perstans

Late stage of limited ZS (Morphea) with leading Atrophie  

  • Acrodermatitis chronica atrophicans  
  • Lipodystrophie  
  • Lichen sclerosus: (important DD for the small spotted circumscript scleroderma; histology is helpful but not always conclusive; circumscript scleroderma never affects the mucous membranes of the genitalia in contrast to Lichen sclerosus et atrophicus)  
  • Scar
  • Necrobiosis lipoidica (histology is diagnostic in connection with the clinical findings).

Generalized ZS  

  • systemic scleroderma (in circumscribed scleroderma, ANA and organ involvement are missing)  
  • Pseudosklerodermien  
  • Scleroderma adultorum Buschke  
  • Skleromyxödem  
  • sclerodermiform graft-versus-host disease  
  • Mischkollagenose  
  • nephrogenic systemic fibrosis (leading symptoms: renal insufficiency, rapid progression, use of gadolinium in MRI examinations).

Linear CS of the type en coup de sabre  

  • Pannikulitiden  
  • progressive partial Lipodystrophie  
  • focal dermal Hypoplasie  
  • Steroid atrophy
  • Lupus erythematosus profundus

Complication(s)
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  • In childhood, growth disturbances in the affected body part can occur in type II and III, especially in herds spanning several joints (see below scleroderma, circumscripts juvenile).
  • Carpal tunnel syndrome, movement restrictions (especially in striated chronic cutaneous scleroderma)
  • Association with other autoimmunological and rheumatological diseases, especially psoriasis vulgaris, systemic lupus erythematosus, multiple sclerosis and vitiligo
  • genital lichen sclerosus

Therapy
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Physiotherapy: Lymphatic drainage, massage, physiotherapy are helpful. Especially in linear, inter-joint forms, the joint mobility must be maintained by physical therapy. Biomechanical stimulation (BMS) supports the promotion of blood circulation and deep massage with loosening of the tissue.

General therapy
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  • Avoidance of local pressure and injuries (e.g. tight trouser waistband, pressing shoes on the back of the foot) Permanent pressure can lead to the formation of new foci if scleroderma is present.
  • Physiotherapy: Studies on the efficiency of physiotherapy in circumscribed scleroderma exist from various sources. for various reasons do not exist. Nevertheless, the measures are an important accompanying component in the multimodal treatment of the disease and are frequently used in clinical routine.
    • Especially the joint-transcending linear circumscript scleroderma should be treated physiotherapeutically.
    • Connective tissue massage and manual lymphatic drainage can be performed in the sclerotic stage accompanying system therapy or following system therapy (1-2x/ week for 3-6 months)
    • Physiotherapy and muscle building are absolutely necessary for the linear subtype of the extremities.

External therapy
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  • Glucocorticoids: Topical steroids are particularly effective in the plaque type in an active phase. Duration of therapy: about 3 months, medium to high potency topical steroids should be applied strictly lesionally 1-2 times/day.
  • Intralesional glucocorticoid applications are usually only performed in the rare linear subtype en coup de sabre in the active marginal area. Most frequently, triamcinolone acetonide 10-40 mg diluted with lidocaine 1:2 - 1:4 is injected intralesionally.
  • Vitamin D 3 analogues ( calcipotriol or tacalcitol) can have a tissue softening effect. Creams and lotions containing urea (Eucerin Urea Lotion, Lipoderm Urea) or evening primrose seed oil (Eucerin Omega 12% Lotion, Lipoderm Omega) are suitable for the care of dry, vulnerable skin.
  • Topical calcineurin inhibitors: Smaller pilot studies and case reports describe the successful application of Tacrolimus 0.1% under occlusion in morphea. The effectiveness of this therapy approach is not sufficiently secured.
  • Imiquimod: There are few case series and some casuistics. After 3-6 months of therapy a clear improvement of dyspigmentation, sclerosis and erythema was described. The effectiveness of this therapeutic approach is not sufficiently proven.

Radiation therapy
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  • Consistent irradiation with UVA1 in an ascending dosage, starting with 5 J/cm² up to 20 J/cm², is recommended. The inflammatory component can thus be controlled after only 10-15 treatments. If sclerosis has already occurred, UVA1 irradiation should be maintained at the above-mentioned dose until the tissue has become softer. In addition to the anti-inflammatory effect, UVA1 irradiation leads to the release of collagenase with corresponding softening of the collagenous connective tissue.
  • In adulthood, a high-dose UVA1 therapy can be carried out, taking into account the side effects. This may also help to reduce sclerosis and hypopigmentation.
  • In a controlled study on phototherapy in circumscribed scleroderma, it was shown that UVA1 is significantly more effective than narrow band UVB phototherapy.

Internal therapy
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  • In the linear subtype with facial infestation or joint involvement, or at risk of longitudinal growth, therapy with methotrexate in combination with systemic glucocorticoid pulse therapy (prednisolone 1.0 g i.v. over 3 days/ 6 monthly therapy regimen) should be started early.
  • In generalized circumscript scleroderma, high-dose protocols with steroid pulse therapy (1.0 g prednisolon/day i.v. for 3 days) in combination with MTX continuous therapy (15 mg/week MTX p.o.) were used with good success. Also with this variant the therapy should be started as early as possible.
  • Encouraging results were achieved with low-dose methotrexate (mono) therapy (15 mg/week MTX p.o. over a period of 24 weeks).
  • The previously frequently used systemic therapy with penicillin G 10 Mega IU/day i.v. over 10 days (3 cycles at intervals of 4 weeks) has now been largely abandoned. Exception: Especially in the presence of a Borrelia infection.
  • D-Penicillamine: Still maintains a certain status in international literature (personal experience is negative).

Operative therapie
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  • Timely surgical intervention is indicated in cases of sclerotic growth disorders, dermatogenic contracture, scarred alopecia.
  • In the facial area, a specialized center for oral and maxillofacial surgery should be consulted, and if joints and extremities are involved, a specialized pediatric surgeon or orthopedist should be consulted.

Progression/forecast
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Generally active course over several years, after which the disease burns out, leaving the sclerosis or atrophy that has developed.

25% of patients suffer a recurrence, which can occur even after years of latency. The linear form shows a particularly high recurrence rate.

Naturopathy
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Dulcamaris products, e.g. Cefabene ointment or Dermatodoron, have anti-inflammatory effects.

Note(s)
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In the Anglo-American literature the beriff Morphea is increasingly used instead of circumscribed scleroderma.

Literature
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  1. AWF guideline (2008) Diagnosis and therapy of circumscritic scleroderma. Register number 013 - 066 Classification S1
  2. Gelber AC, Wigley FM (2002) Disease severity as a predictor of outcome in scleroderma. Lancet 359: 277-279
  3. Ghoreschi K, Rocken M (2002) Phototherapy of sclerosing skin diseases. Dermatology 205: 219-220
  4. Hercogova J (2002) Borrelia burgdorferi: a protagonist in Lyme disease, a bystander in morphoea? J Eur Acad Dermatol Venereol 16: 98-99
  5. Khatri S et al (2019) Autoantibodies in morphea: An update. Front Immunol 10:1487.
  6. Kreuter A et al (2006) Ultraviolet A1 phototherapy decreases inhibitory SMAD7 gene expression in localized scleroderma. Arch Dermatol Res 298: 265-272
  7. Kreuter A et al (2006) Ultraviolet A1-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma. Br J Dermatol155: 600-607
  8. Kreuter A et al (2006) A randomized controlled study of low-dose UVA1, medium-dose UVA1, and narrowband UVB phototherapy in the treatment of localized scleroderma. J Am Acad Dermatol 54: 440-407
  9. Kreuter A et al (2005) Pulsed high-dose corticosteroids combined with low-dose methotrexate in severe localized scleroderma. Arch Dermatol 141: 847-852
  10. Leitenberger J et al.(2009) Distinct autoimmune syndromes in morphea. Arch Dermatol 145: 545-550
  11. Lutz V et al. (2011) High frequency of general lichen sclerosus in a prospective series of 76 patients with morphea. Arch Dermatol 2011: 305
  12. Marzano AV et al (2003) Localized scleroderma in adults and children. Clinical and laboratory investigations on 239 cases. Eur J Dermatol 13: 171-17
  13. Mertens JS et al.(2015) Disease recurrence in localized scleroderma: a retrospective analysis of 344 patients with paediatric- or adult-onset disease. Br J Dermatol 172:722-728
  14. Nagai Y et al (2002) Unilateral generalized morphea in childhood. J Dermatol 29: 435-438
  15. Seyger M et al (1998) Low-dose methotrexate in the treatment of widespread morphea. J Am Acad Dermatol 39: 220-225
  16. Sehgal VN et al (2002) Localized scleroderma/morphea. Int J Dermatol 41: 467-475
  17. Stücker M et al (1999) Severe course of mutating pansclerotic circumskripten scleroderma in childhood. Dermatologist 50: 131-135
  18. Toledano C et al (2008) Localized scleroderma: a series of 52 patients. Eur J Intern Med 20:331-336
  19. Uziel Y et al (2000) Methotrexate and corticosteroid therapy for pediatric localized scleroderma. J Pediatr 136: 91-95
  20. Weibel L et al (2006) Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphea) in children. Br J Dermatol 155: 1013-1020
  21. Yazdanpanah MJ et al.(2015) Frequency of Borrelia in Morphea Lesion by Polymerase Chain Reaction in Northeastof Iran.Jundishapur J Microbiol 8:e19730.
  22. Zulian F et al (2005) Localized scleroderma in childhood is not just a skin disease. Arthritis&Rheumatism 52: 2873-2881

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Last updated on: 16.10.2021