Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis

Updated: Feb 23, 2018
  • Author: Mariana J Kaplan, MD; Chief Editor: Herbert S Diamond, MD  more...
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Overview

Practice Essentials

Localized fibrosing disorders include a spectrum of rare conditions that frequently begin in childhood.  Localized fibrosing disorders can be classified into several subtypes that include morphea, generalized morphea, and linear scleroderma, in which facial involvement is termed en coup de sabre. Linear scleroderma and morphea can coexist in the same patient. Other fibrosing conditions mentioned in this article include retroperitoneal fibrosis, mediastinal fibrosis, and Dupuytren contracture.

The causes of localized fibrosing disorders are unknown. Genetic, infectious, and autoimmune mechanisms have been proposed. Neoplasms, infections, trauma, aortic aneurysms, and ergot have been associated with retroperitoneal fibrosis.

Treatment varies with the specific condition. Although the clinical course of these diseases is often benign, widespread lesions and disabling joint contractures may lead to significant complications.

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Pathophysiology

The exact pathogenesis is unknown. However, extensive extracellular matrix (collagen) formation and autoimmune dysfunction are thought to be key pathogenic processes. Localized fibrosing disorders include several clinical and histopathological conditions that are similar to the skin involvement of systemic sclerosis, but the systemic features are absent. These lesions are characterized by circumscribed fibrotic areas involving different levels of the dermis, subcutis, and, sometimes, underlying soft tissue and bone. Fibrosis is a result of excessive collagen synthesis and decreased degradation.

Transforming growth factor-beta 1 (TGF-beta1) has been shown to increase the expression of several collagen types and other extracellular matrix components in morphea and SSc. Additionally, TGF-beta1 has inhibitory effects on matrix degradation. However, the processes leading to excessive TGF-beta1 synthesis in morphea remain poorly understood. [1]  

Multiple environmental factors have been proposed to be involved in morphea pathogenesis. The role of friction, long-term pressure, or mechanical factors such as vaccination injection have been reported in 13–16% of morphea patients. [1] Morphea is also an uncommon complication following radiation therapy. [2]

Autoimmunity is likely involved in the pathogenesis because of the presence of autoantibodies in a proportion of the morphea patients and the presence of concomitant autoimmune diseases in morphea patients and their relatives. However, low concordance rates of autoimmune diseases in monozygotic twins suggest additional pathogenic mechanisms besides genetic factors.

MicroRNAs (miRNAs) are short non-coding RNAs of 18–23 nucleotides that bind messenger RNAs (mRNAs) and thereby inhibit their translation or induce mRNA degradation. A study reported upregulation of miRNA-155 in SSc and morphea skin. [3]  

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Etiology

The causes of localized fibrosing disorders are unknown. Suggested causes include genetic, infectious, and autoimmune mechanisms. Neoplasms, infections, trauma, aortic aneurysms, and ergot have been associated with retroperitoneal fibrosis.

Autoantibodies are frequently seen in localized scleroderma, particularly antinuclear antibodies and antibodies to single-stranded DNA and histones.

Environmental agents (eg, L-tryptophan, vinyl chloride, bleomycin, methysergide, ergot, bromocriptine, radiation) can cause a morphealike picture. Methysergide is also associated with the development of retroperitoneal fibrosis. Other drugs that can trigger this condition include phenacetin, hydralazine, and propranolol.

Infections (eg, varicella, measles, Epstein-Barr virus infection, borreliosis) may precede the onset of morphea. Histoplasma capsulatum infection has been associated with the development of mediastinal fibrosis.

Vaccination (bacille Calmette-Guérin [BCG]) has also been reported to precede the onset of morphea, and trauma has been considered a possible triggering event in these conditions.

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Epidemiology

The frequency of morphea ranges from 3.4 cases per million adults to 2.7 cases per 100,000 population, depending on the report. [1] Morphea seems to be more prevalent in whites than in blacks. Morphea is more common in women than in men, with a female-to-male ratio of 2.4-5.0:1 [1] and may appear or worsen during pregnancy. The incidence peaks in children between 7 and 11 years and adults between 44–47 years. [1]

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Prognosis

In general, localized and regional fibrosing disorders carry a good prognosis. Plaquelike lesions tend to improve with time. The duration of the activity usually is 3-5 years, but some lesions persist longer. Residual pigmentation persists long term in about one-third of the patients. Linear lesions tend to persist longer than plaque lesions. Contractures may limit joint movements and may lead to clawing of the hands. Facial hemiatrophy persists.

In mediastinal and retroperitoneal fibrosis, the prognosis is related to the amount of irreversible obstruction and complications are related to obstruction of vascular structures, bronchi, or ureters.

Individuals with the severe inflammatory subtypes, en coup de sabre linear scleroderma, or Parry-Romberg disease can have severe functional limitations. Loss of eyebrow or eyelashes, ptosis, pseudooculomotor palsy, uveitis, asymmetry of the tongue, and altered dentition and dental caries can occur in patients with morphea en coup de sabre. Overt seizures may occur in patients with Parry-Romberg syndrome.

Children are more likely than adults to develop localized forms of scleroderma. Because of the impact on growth, these lesions can result in major facial or limb asymmetry, flexion contractures, and disability. 

Localized fibrosing disorders are only rarely life threatening, but they can severely affect quality of life, particularly in children. Psychosocial problems related to adjusting to deformities and disfiguration can occur.

Although the clinical course of the disease is often benign, widespread lesions and disabling joint contractures may lead to significant complications. Joint contractures, deformities, and severe limb atrophy can occur in patients with linear scleroderma. A 1.5- to 7-cm leg length discrepancy occurs in 20% of patients with linear scleroderma. Severe atrophy of underlying muscle and bone also can occur. Arthralgias, osteoporosis, flexion contractures, and other bone changes are common.

Aplastic anemia, thrombocytopenia, and hemolytic anemia have been reported in patients with eosinophilic fasciitis. Intense pain may be present, particularly in disabling pansclerotic morphea of children and in en coup de sabre lesions, probably due to cutaneous nerve involvement.

In patients with generalized morphea, contractures may occur in limbs, and mobility may be restricted. Marked chest wall involvement may cause difficulty in breathing due to constriction of the thorax.

Complications in Dupuytren contracture are related to progressive hand deformities.

 

 

 

 

 

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