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

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

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.

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]  

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.

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]

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.

 

 

 

 

 

 

Presentation

History

The clinical presentation of morphea varies depending on the level of tissue involvement and extent of the lesions. The diagnosis is based more on physical examination than on history. Certain features, including localization of the lesions, help the clinician increase the index of suspicion for a specific diagnosis. A common feature of morphea is skin thickening. Internal organ involvement is not evident in most patients with morphea.

Some patients present with associated arthralgias, foot and hand deformities, central nervous system abnormalities, intermittent abdominal pain, and periosteal erosions and osteolysis.

Spina bifida is found in almost 33% of patients with morphea. Associated cutaneous pathologies include alopecia areata, vitiligo, dystrophy of the nails, and ichthyosis. Occasionally, localized morpheic lesions occur in the uninvolved skin of patients with progressive systemic sclerosis. Morphea has been reported in association with the following disorders:

Physical

Plaque morphea

Superficial morphea are often confined to the dermis, as depicted in the images below, and occasionally to the superficial panniculus. Subsets include the following:

This photograph shows morphea en plaque on the tru This photograph shows morphea en plaque on the trunk of a patient. There is a distinctive border separating the plaque from the surrounding normal skin (reproduced with permission of Mayo Clinic Proceedings).
This photograph shows generalized morphea on the t This photograph shows generalized morphea on the trunk of a patient (reproduced with permission from Mayo Clinic Proceedings).

Morphea en plaque

This is the most prevalent form of this group. It involves only 1 or 2 anatomic sites, usually the trunk. The disease is characterized by one or more circular areas of induration, usually larger than 1 cm in diameter, with varying degrees of pigment changes.

An erythematous or violaceous halo (lilac ring), which is often evident during early disease, corresponds with an inflammatory state. As the disease progresses, the skin becomes sclerotic. As the inflammation subsides, the center of the lesion becomes whitish. After months to years, the skin softens and becomes atrophic, and a residual area of hypopigmentation or hyperpigmentation might occur. Distinctive borders usually separate the plaques from the normal surrounding skin.

Guttate morphea

This subset usually occurs on the upper trunk. Typically, it presents as multiple oval lesions between 2-10 mm in diameter. The lesions often manifest as faint erythema, followed by mild induration and hypopigmentation or hyperpigmentation.

Keloid morphea

This presents as nodules that resemble keloids in the presence of typical morphea.

Lichen sclerosus et atrophicus

This is characterized by shiny white plaques often preceded by violaceous discoloration of the skin. This subset has a predilection for the anogenital area and has an increased association with autoimmune-related diseases (eg, vitiligo, alopecia areata).

Atrophoderma of Pasini and Pierini

This presents as asymptomatic, hyperpigmented atrophic patches with well-demarcated "cliff drop borders" on the trunk. No pronounced inflammatory or sclerotic changes are present. The course is chronic, with spontaneous resolution usually after 10 years.

Generalized morphea

This occurs when individual plaques of morphea become confluent lesions. It can affect more than two anatomic sites, including the upper trunk, breasts, abdomen, and upper thighs. Arms, legs, face, neck, and scalp may also be involved.

Bullae may develop in localized areas, particularly around the abdomen. Keratoses and calcinosis may occur. Contractures may occur in limbs, and mobility may be restricted.

Bullous morphea

This is characterized by tense subepidermal bullae in the presence of typical morphea or morphea profunda. The lesions can occur on the face, neck, trunk, or extremities and may be superficial or extend deep into the dermis.

Linear scleroderma

This is characterized by one or more linear streaks and induration that can involve dermis, subcutaneous tissue, muscle, and bone. It occurs on the extremities, face, or scalp of children and adolescents. It is subdivided into subgroups including linear scleroderma, lesions en coup de sabre, and progressive hemifacial atrophy (Parry-Romberg syndrome).

Linear scleroderma

This is characterized by discrete linear induration that primarily affects the extremities. In more than 90% of patients, the involvement is unilateral. Linear scleroderma is complicated by deformities, joint contractures, and severe limb atrophy. The process can affect the growth of bony structures.

Lesions en coup de sabre

If the face or scalp is affected with linear scleroderma, the involvement is often compared to a stroke from a sword (sabre). The lesions start with contractions and firmness of the skin over the affected area. Then, an ivory, irregular, sclerotic plaque with hyperpigmentation at the edge develops.

Progressive hemifacial atrophy (Parry-Romberg syndrome)

This subtype results in hemiatrophy of the face. The primary lesions occur in the subcutaneous tissue, muscle, and bone. The disease usually begins in the first 2 decades of life.[4]

Deep morphea

This primarily involves the deep dermis, subcutaneous tissue, fascia, or superficial muscle. The lesions are more diffuse than in linear scleroderma and do not demonstrate a linear pattern. Subtypes include subcutaneous morphea, morphea profunda, disabling pansclerotic morphea of childhood, and eosinophilic fasciitis.

Subcutaneous morphea

It primarily involves the panniculus or subcutaneous tissue. The onset of sclerosis is usually rapid, occurring during a period of several months. This is a more of an inflammatory condition than other types of morphea.

Morphea profunda

The entire skin feels thickened, bound down, and taut. Deep sclerosis of the skin develops. Onset usually occurs before age 14 years. The extensor aspect of the extremities and trunk develops sclerotic plaques that extend deep into the subcutaneous tissue, fascia, muscle, and bone. The lilac ring is usually absent.

Disabling pansclerotic morphea of childhood

This is an aggressive and mutilating variant of morphea. It is characterized by generalized, full-thickness involvement of the trunk, extremities, face, and scalp. The fingertips and toes are usually spared.

Eosinophilic fasciitis

This condition is characterized by a painful peau d'orange appearance involving the extremities, proximal to the hands and feet. The fascia is the predominant level of involvement. The groove sign (linear depressions along the course of veins), concurrent plaque morphea, and peripheral eosinophilia may be present. In one study, 28% of patients had a history of recent trauma or exercise.[5] The natural course is not well defined, but the disorder may spontaneously regress or remain unchanged for years.

Regional fibrosing disorders

Mediastinal fibrosis is characterized by excessive perinodal fibrotic proliferation that invades and destroys normal mediastinal structures. It can coexist with retroperitoneal fibrosis. It is considered the most serious late complication of remote Histoplasma capsulatum infection. Tuberculosis has been considered another triggering agent. Mediastinal hemorrhage and methysergide use also can trigger mediastinal fibrosis.

Patients with mediastinal fibrosis can present with pleuritic chest pain, malaise, and pain and stiffness in the thoracic spine. Other symptoms include dyspnea, cough, hemoptysis, and superior vena caval obstruction. The fibrotic process may accrue over prolonged periods and may extend within the lumina of critical mediastinal structures to produce complete occlusion. Patients may develop severe stenosis of the trachea, carina, or mainstem bronchi.

An accentuated pulmonic component of the second heart sound, wheezing, and localized murmur are among the most common physical findings. Thoracotomy may be required for histologic diagnosis. Successful superior vena cava bypass surgery has been described. Corticosteroid therapy has been effective in some reported cases.

Retroperitoneal fibrosis, or Ormond disease, is a rare inflammatory fibrosing disorder that leads to compression of the ureter, vena cava, nerves, and aorta. The disorder is about twice as common in males as in females, and the peak age at onset is in the fifth and sixth decades of life. The course is usually slowly progressive.

Low back pain is the most common symptom. Weight loss and fever are common. The most common clinical presentation of retroperitoneal fibrosis is renal dysfunction due to obstruction of the ureters. The retroperitoneal involvement may spread to the deep structures in the pelvis. Patients with retroperitoneal fibrosis can present with upper gastrointestinal bleeding and ascites due to complications of portal hypertension. Some patients may present with signs and symptoms of pulmonary hypertension associated with pulmonary arterial and venous obstruction.

Retroperitoneal fibrosis has been associated with the use of certain medications, including methysergide, ergotamine, pergolide (withdrawn from US market March 29, 2007), hydralazine, and methyldopa. Associated diseases include the following:

  • Atherosclerotic disease of the aorta (abdominal aortic aneurysm)
  • Systemic lupus erythematosus
  • Vasculitis
  • Scleroderma
  • Biliary cirrhosis
  • Malignancy

Dupuytren contracture consists of a thickening and shortening of the palmar fascia. Thick, cordlike superficial fibrous tissue, which can be felt in the palm, causes a contracture, usually of the fourth finger. The fifth, third, and second fingers are involved in decreasing order of frequency. Initial lesions might show dimpling or puckering of the skin over the involved fascia. Dupuytren contracture occurs predominantly in whites and is more common in Europe. The condition is 5 times more common in men. A gradual increase in incidence occurs with age. An association with diabetes and liver disease has been reported.

 

DDx

Diagnostic Considerations

Distinguishing eosinophilic fasciitis (ET) from systemic sclerosis (SSc) is important because corticosteroids are first-line therapy for EF, but are generally avoided in patients with SSc due to associations with renal crisis. Furthermore, early treatment of EF has been reported to improved outcomes. Both disorders frequently present with induration of the extremities but visceral involvement in EF is generally limited to hematologic abnormalities, and thus an extensive systemic workup is not indicated as it is in SSc. Clinically, nailfold capillary changes and Raynaud phenomenon are typically absent in EF, unlike in SSc, and skin tightening on the distal digits is lacking.[5]  

Other problems to consider in the differential diagnosis include the following:

  • Acrodermatitis chronica atrophicans

  • Bleomycin exposure

  • Bromocriptine exposure

  • Carcinoid syndrome

  • Panniculitis

  • Ergot exposure

  • Localized lipoatrophies

  • Methysergide exposure

  • Phenylketonuria

  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes)

  • Poikiloderma

  • Porphyria cutanea tarda

  • Scleredema

  • Scleromyxedema

  • Vitamin K injection

Differential Diagnoses

 

Workup

Approach Considerations

Early evaluation for prevention and treatment of joint and muscle contractures and deformities is important. 

In retroperitoneal fibrosis, laboratory abnormalities are nonspecific, including an elevated erythrocyte sedimentation rate. The diagnosis is often suggested by findings on intravenous pyelography. Ultrasonography, CT scanning, and MRI are useful, showing a fibrotic paraaortic mass. Gallium scintigraphy may help assess activity of inflammation. Multiple deep biopsies may be required to distinguish this condition from malignancy.

Laboratory Studies

Currently, no reliable laboratory markers are available for assessing disease activity. Antinuclear antibodies can be detected in 46-80% of patients with morphea. The most common pattern is homogeneous, but this is nonspecific.

The erythrocyte sedimentation rate may be increased in eosinophilic fasciitis, in some forms of linear and localized morphea, and in mediastinal and retroperitoneal fibrosis.

A polyclonal gammopathy may occur in patients with morphea or eosinophilic fasciitis.

Imaging Studies

Computed tomographic scanning and magnetic resonance imaging of the chest and abdomen are helpful in evaluating patients with mediastinal and retroperitoneal fibrosis, respectively. See the image below.

 

CT scan of the abdomen showing the typical paraaor CT scan of the abdomen showing the typical paraaortic mass of retroperitoneal fibrosis.

Procedures

A biopsy of the lesion is considered the criterion standard. For plaque, generalized, and bullous morphea, a deep punch biopsy is often sufficient. For linear and deep forms of morphea, an excisional biopsy of the skin including the dermis, panniculus, and fascia is preferred. Biopsies of fibrotic lesions of the mediastinum and retroperitoneum are useful in establishing a diagnosis in regional fibrosing disorders and for ruling out infection or malignancy.

Histologic Findings

Dermal fibrosis characterizes the cutaneous lesions of both local and systemic forms of scleroderma. The lesion seen in localized sclerosing conditions is characterized by infiltration of lymphocytes, mast cells, plasma cells, and eosinophils with excess collagen deposition extending into the dermis, the subcutaneous fat, and, in some forms, deeper structures.

The focus of morphea seems to be collagen fibers, which become altered with thickening and hyalinization. The histology of mediastinal and retroperitoneal fibrosis consists of foci of chronic inflammatory infiltrates at the periphery of the lesion with lymphocytes and macrophages and a central region of fibrosis.

Histopathology of progressive hemifacial atrophy (PHA) shows homogenized dermal sclerosis, fat atrophy, decrease in adnexal structures, and perivascular plasma cells and lymphocytes.[4]

 

Treatment

Approach Considerations

Most patients with plaque morphea experience spontaneous remission and require no specific treatment. Treatment depends entirely on the severity of the findings. Intralesional injections of corticosteroids might be helpful in early stages. The progression of Dupuytren contracture varies, ranging from little or no change over many years to rapid progression and complete flexion contracture of one or more digits.

The treatment of mediastinal and retroperitoneal fibrosis has not been well studied. Surgical treatment is often highly successful. Steroid therapy may be useful in the cases detected before significant obstruction has occurred. Azathioprine, cyclophosphamide, and tamoxifen have been used as well, with apparent success. The long-term outlook is fairly good if the disease is recognized early before irreversible obstructive lesions have occurred. Most deaths are secondary to renal failure.

Medical Care

Threapy for specific disorders is as follows:

  • Progressive hemifacial atrophy (PHA) – Methotrexate (MTX) is the standard therapy for active  PHA. A long course of therapy is typically required, as relapse is frequently seen with shorter courses of therapy. Current evidence supports a 12-24 month course of methotrexate being most effective in inducing prolonged remission. MTX is often combined with oral prednisone over the first three months because MTX has a delayed effect on inflammation and fibrosis. [4]  If the lesions spread (as in generalized morphea), anti-inflammatory or immunosuppressive medications may be indicated.
  • Morphea – Although numerous therapeutic agents have been used for morphea, treatment remains unsatisfactory. Daily antimalarial agents may be beneficial, especially when lesions are highly inflammatory.
  • Linear scleroderma and deep morphea – Aggressive treatment, including systemic corticosteroids, may be necessary. Topical corticosteroids may also be useful. Occasionally, other disease-modifying agents, including d-penicillamine, azathioprine, sulfasalazine, methotrexate, and cyclophosphamide, are necessary to control a severe inflammatory process. Plasmapheresis may be useful in some patients, but no randomized controlled trials have been published.

One study reported that occlusive treatment with tacrolimus ointment can be useful in localized scleroderma.[6]  Imiquimod has been suggested as a potential topical treatment for morphea and fibromatoses, but more studies are needed.[7]

Corticosteroids are considered first-line therapy for eosinophilic fasciitis (ET), however prolonged use is often required. In one study, complete response was more likely with a combination of corticosteroids and methotrexate (64%) than corticosteroid monotherapy (30%).[5]  

Phototherapy

Several phototherapy modalities including ultraviolet B (UVB), psoralen plus broadband UVA (PUVA), broadband UVA, and UVA1 have been investigated for morphea. Lower wave length phototherapy (UVA) has emerged as the preferred modality because of its greater potency of tissue penetration than UVB and lower risk of sunburn than broadband UVA. Evidence suggests that UVA1 effects are dose-related and superior results for high-dose-UVA compared with low-dose-UVA have been reported.[1]   

There are no internationally agreed definitions of treatment doses but in general, categories are as follows[8] :

  • Very low dose: 2</sup> i
  • Low dose: 10-29 J/cm 2 
  • Medium dose: 30-59 J/cm 2 
  • High dose: 60-130 J/cm 2 

Long-term outcome of UVA1 therapy is unclear. In a study of 37 adults who underwent successful UVA1 therapy, 2-year and 3-year recurrence rates of 44.5 and 48.4%, respectively. Active morphea for more than 1 year prior to UVA treatment significantly increased the risk of recurrence.[9]

Acute adverse effects of UVA1 are minimal, with mild tanning or skin pigmentation being the most common. Uncommon acute adverse effects include reactivation of herpes simplex, cholinergic urticaria, and transient and reversible changes in the appearance of moles The risk of long-term adverse effects, particularly skin cancer, is unknown.[8]

 

 

Surgical Care

Tendon-lengthening procedures and surgical release of joint contractures are sometimes necessary. Amputation may be necessary as a consequence of severe flexural deformity.

Often, patients with en coup de sabre or Parry-Romberg syndrome require surgical reconstruction of the face and scalp. Reports indicate that en coup de sabre lesions have been repaired effectively with a combination of an expanded skin flap and a hydroxyapatite implant.

When actual contractures occur in Dupuytren contracture, surgical intervention is desirable. Limited fasciotomy is effective in most instances. More radical procedures, including amputation, are necessary in rare cases. Palmar fasciotomy is a useful and more benign procedure.

Surgical management is often required to treat the complications of both retroperitoneal and mediastinal fibrosis.

Consultations

Consultations to consider include the following:

  • Physical therapy is very important for patients prone to develop joint and muscle contractures and deformities. Joint mobility should be maintained. Heat treatment and massage might be helpful.
  • Psychotherapy for people with deformities and disfiguration is very important.
  • Cases that involve children with severe facial deformities should be referred to a plastic surgeon for prompt evaluation and consultation about possible treatment.
  • Early evaluation by a reconstructive or plastic surgeon is important for patients with en coup de sabre lesions or Parry-Romberg disease.
  • Evaluation by a hand surgeon may be indicated in patients with Dupuytren contracture for consideration of releasing the contractures.
  • Surgical consultation may be considered in patients with mediastinal and retroperitoneal fibrosis if obstructive lesions occur.

Long-Term Monitoring

Periodic follow-up is recommended to detect early spread of lesions or other chronic complications.

 

Medication

Medication Summary

Glucocorticoids can be used systemically, topically in ointment form, or under occlusive dressings. Diluted triamcinolone acetonide suspension of 1:3 to 1:5 given by intralesional injection has been suggested. Repeated infiltrations are recommended every 3-4 weeks. Ointments containing heparin or heparinoids may also be helpful.

Linear scleroderma in children has effectively been treated with oral calcitriol. The use of phenytoin has been advocated, especially for linear morphea. Long-term treatment with oral p-aminobenzoate has been suggested, but the results are unclear.

Topical tocoretinate for 6 months to 3 years may be beneficial for treating skin sclerosis.[10] The following agents have been reported to be beneficial in morphea:

  • D-penicillamine
  • Corticosteroids
  • Phenytoin
  • Aminobenzoate potassium
  • Dimethyl sulfoxide
  • Vitamin E
  • Disodium edetate
  • Sulfasalazine
  • Cyclofenil
  • Methotrexate
  • Colchicine
  • Antimalarials
  • Azathioprine
  • Griseofulvin
  • Penicillin
  • Chlorambucil
  • Cyclophosphamide
  • Etretinate
  • Isotretinoin
  • Interferon alfa and gamma

No treatment seems to alter the natural course of localized scleroderma, but reports indicate that moderate doses of systemic or locally injected corticosteroids, d-penicillamine, and photochemotherapy with 8-methoxypsolaren have been helpful in decreasing the degree of inflammation and fibrosis.

Antimalarials

Class Summary

These agents have anti-inflammatory properties and inhibit multiple functions of phagocytes, including reactive oxygen species release.

Hydroxychloroquine (Plaquenil)

Treats malaria, rheumatoid arthritis, systemic lupus erythematosus, and juvenile chronic arthritis. Use in localized fibrosing disorders has not been well characterized, but several reports indicate some efficacy. Response to antimalarials is slow, so it can take up to 6 months for full effect.

Corticosteroids

Class Summary

These agents have potent anti-inflammatory and immunosuppressive properties. They inhibit lymphocyte proliferation and delayed-type hypersensitivity and cause changes in WBC traffic and Fc receptor suppression.

Prednisone (Orasone, Deltasone, Sterapred)

Constitutes main therapy for multiple inflammatory and autoimmune disorders including vasculitis, systemic lupus erythematosus, inflammatory myopathies, and polymyalgia rheumatica. May be useful in localized and regional fibrosing disorders by inhibiting inflammatory response.

Triamcinolone (Aristocort)

Can be helpful in inhibiting inflammation and fibrosis in localized fibrosing conditions. Repeated administrations might be necessary.

Immunosuppressives/disease-modifying antirheumatic drugs

Class Summary

These agents have anti-inflammatory and immunosuppressive properties. Some drugs may have antifibrotic effects.

D-Penicillamine (Cuprimine)

Used to treat rheumatoid arthritis and shown to have some benefit in systemic sclerosis. Its mode of action is unknown, but seems to modulate the immune system via sulfhydryl exchange reactions in various cells.

Azathioprine (Imuran)

Purine analog and derivative of 6-mercaptopurine. Has immunosuppressive effects by inhibiting purine synthesis in cells. Used for treating systemic lupus erythematosus, rheumatoid arthritis, vasculitis, and inflammatory myopathies and preventing allograft rejection.

Sulfasalazine (Azulfidine)

Sulfonamide derivative with anti-inflammatory properties. Useful for treating rheumatoid arthritis, spondyloarthropathies, and inflammatory bowel disease. Effects on localized fibrosing conditions are not well characterized.

Methotrexate (Rheumatrex)

This drug reversibly inhibits dihydrofolate reductase; limits the availability of 1-carbon fragments necessary for synthesis of purines and the conversion of deoxyuridylate to thymidylate in the synthesis of DNA and cell reproduction. Extensively used for cancer treatment, rheumatoid arthritis, psoriasis, and as a steroid-sparing agent in various autoimmune conditions.

Cyclophosphamide (Cytoxan, Neosar)

Synthetic nitrogen mustard alkylating agent used for treating severe lupus complications, vasculitis, refractory rheumatoid arthritis, scleroderma lung disease, and myopathies. Its role in localized forms of fibrosis has not been well characterized. It is indicated only for severe inflammatory lesions that do not respond to other agents.

Colchicine

Inhibits microtubule formation in leukocytes and decreases joint inflammation. Drug has no direct analgesic properties. Useful in gout, skin vasculitis, and Behçet disease. Has been advocated to have an antifibrotic effect with potential therapeutic implications in generalized or localized fibrosing disorders.

Tacrolimus (Prograft, Protopic)

Used to treat atopic dermatitis and for prophylaxis of renal and kidney transplant rejection.

Topical Skin Product

Class Summary

Agents such as imiquimod may induce mediators of immune processes.

Imiquimod (Aldara)

Topical antiviral agent. Induces secretion of interferon alpha and other cytokines; mechanism of action is unknown.