AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Localized fibrosing disorders include a spectrum of rare conditions that frequently begin in childhood. These lesions are characterized by circumscribed fibrotic areas involving different levels of the dermis, subcutis, and, sometimes, underlying soft tissue and bone. Although the clinical course of the disease often is benign, widespread lesions and disabling joint contractures may lead to significant complications.

Pathophysiology

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. 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.

Frequency

United States

The frequency of morphea ranges between 3.4 cases per million adults to 2.7 cases per 100,000 population, depending on the report.

International

No particular geographic distribution has been noted.

Mortality/Morbidity

• The clinical course of the disease is often benign, but widespread lesions and disabling joint contractures may lead to significant complications.
• Localized fibrosing disorders are only rarely life threatening, but they can severely affect quality of life, particularly in children.

Race

• Morphea seems to be more prevalent in whites than in blacks.

Sex

• Morphea is more common in women than in men, with a female-to-male ratio of 3-4:1.
• Morphea may appear or worsen during pregnancy.

Age

• 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.
• Linear scleroderma tends to affect children and adolescents.
• Morphea en plaque is more common in adults.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 is skin thickening.
• In most patients, there is no evidence of internal organ involvement.
• Some patients might 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 the patients.
• 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 systemic lupus erythematosus, primary biliary cirrhosis, pemphigus, and dermatomyositis.

Physical

• Plaque morphea: Superficial morphea are often confined to the dermis (see Image 1 and Image 2) and occasionally to the superficial panniculus. Subsets include morphea en plaque, guttate morphea, keloid morphea, lichen sclerosus et atrophicus, and atrophoderma of Pasini and Pierini.
• • 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 1 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 often is 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. There is a predilection for the anogenital area. There is higher incidence of 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. There are no pronounced inflammatory or sclerotic changes. 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 2 anatomic sites, including the upper trunk, breasts, abdomen, and upper thighs.
  • Arms, legs, face, neck, and scalp also may 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. The disease 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 will develop.
  • 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.
• 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 usually is rapid, occurring during a period of several months. This is a more inflammatory condition than other types of morphea.
  • Morphea profunda: The entire skin feels thickened, bound down, and taut. Patients develop deep sclerosis of the skin. Onset usually occurs in patients younger than 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 usually is 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 usually are 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 natural course is not well defined, but patients seem to 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 infection by Histoplasma capsulatum. Tuberculosis has been considered another triggering agent. Mediastinal hemorrhage and methysergide use also can trigger this condition.
  • • Patients 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 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 incidence is in the fifth and sixth decades of life. The course usually is slowly progressive in nature.
  • • Low back pain is the most common symptom. Weight loss and fever are common. The most common clinical presentation is renal dysfunction due to obstruction of the ureters. The retroperitoneal involvement may spread to the deep structures in the pelvis. Patients 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.
    • This condition 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 atherosclerotic disease of the aorta (abdominal aortic aneurysm), systemic lupus erythematosus, vasculitis, scleroderma, biliary cirrhosis, and malignancy.
    • Laboratory abnormalities are nonspecific, including an elevated erythrocyte sedimentation rate. The diagnosis is often suggested by findings at intravenous pyelography. Ultrasound, CT scanning, and MRI are useful showing a fibrotic paraaortic mass (see Image 3). Gallium scintigraphy may help assess activity of inflammation. Multiple deep biopsies may be required to distinguish this condition from malignancy.
    • Surgical treatment often is 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.
  • 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 frequent in men. A gradual increase in incidence occurs with age. An association with diabetes and liver disease has been reported.

Causes

• 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 seen frequently 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 also is associated with the development of retroperitoneal fibrosis. Other drugs that can trigger this condition include phenacetin, hydralazine, and propranolol.
  • Infections (varicella, measles, Epstein-Barr virus, and borreliosis, among others) may precede the onset of morphea. Histoplasma capsulatum has been associated with the development of mediastinal fibrosis.
  • Vaccination (bacille Calmette-Guérin [BCG]) also has been reported to precede the onset of morphea, and trauma has been considered a possible triggering event in these conditions.

DIFFERENTIALS

Section 4 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

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

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab 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.
• Erythrocyte sedimentation rate can 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.

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.

TREATMENT

Section 6 of 11  

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• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• 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.
• • In Dupuytren contracture, progression of the disease 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, although corticosteroids, immunosuppressive agents, and tamoxifen appear to be effective.
• If the lesions spread (as in generalized morphea), anti-inflammatory or immunosuppressive medications may be indicated.
• Although numerous therapeutic agents have been used for morphea, treatment remains unsatisfactory.
• Daily antimalarial agents may be beneficial, especially when lesions are highly inflammatory.
• In linear scleroderma and deep morphea, aggressive treatment, including systemic corticosteroids, may be necessary. Topical corticosteroids also can be useful.
• Occasionally, other disease-modifying agents, including d-penicillamine, azathioprine, sulfasalazine, methotrexate, and cyclophosphamide, may be necessary to control a severe inflammatory process.
• Plasmapheresis may be useful in some patients, but no randomized, controlled trials have been published.
• Reports indicate that patients with severe localized scleroderma have been treated successfully with psoralen plus ultraviolet light of the A wave length (PUVA) bath photochemotherapy.
• • Low-dose UVA1 phototherapy can be highly effective for sclerotic plaques, even in patients with advanced localized fibrosing disorders with rapidly evolving lesions despite conventional therapy.
  • Patients usually are irradiated with 20 J/cm² UVA1 for 12 weeks, with a cumulative UVA1 dose of 600 J/cm².
• A recent study reported that occlusive treatment with tacrolimus ointment can be useful in localized scleroderma. Imiquimod has also been suggested as a potential treatment for morphea and fibromatoses, but more studies are needed.

Surgical Care

• Tendon-lengthening procedures and surgical release of joint contractures sometimes are 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, rarely may be necessary. Palmar fasciotomy is a useful and more benign procedure. Surgical management is often required for both retroperitoneal and mediastinal fibrosis to treat the complications.

Consultations

• Patients with the linear and deep types of morphea require physical therapy to prevent joint deformities and skin contractures. Heat treatment and massage might be helpful.
• Psychotherapy for people with deformities and disfiguration is very important.
• 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.

Activity

• Physical therapy is very important for patients prone to develop joint and muscle contractures and deformities. Joint mobility should be maintained.

MEDICATION

Section 7 of 11  

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• Differentials
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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 also may 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. 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, and 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.

Drug Category: Antimalarials

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

Drug Category: Corticosteroids

Have potent anti-inflammatory and immunosuppressive properties. Inhibit lymphocyte proliferation and delayed-type hypersensitivity. Cause changes in WBC traffic and Fc receptor suppression.

Drug Name	Triamcinolone (Aristocort)
Description	Can be helpful in inhibiting inflammation and fibrosis in localized fibrosing conditions. Repeated administrations might be necessary.
Adult Dose	Topical: Apply thin film bid/tid to response Intralesional: Suspension of 1:3-1:5 given by intralesional injection suggested; repeated infiltrations are recommended q3-4wk
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; fungal, viral, and bacterial skin infections
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	A percentage of topical drug might be absorbed systemically; if application is repeated, there may be some systemic effects of the corticosteroids

Drug Category: Immunosuppressives/disease-modifying antirheumatic drugs

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

Drug Name	Azathioprine (Imuran)
Description	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.
Adult Dose	2-3 mg/kg/d PO in single or divided dose Starting dose: 1 mg/kg/d PO; increase depending on clinical and hematologic response and toxicity
Pediatric Dose	2-3 mg/kg/d PO in single or divided dose Starting dose: 1 mg/kg/d PO; increase depending on clinical and hematologic response, and toxicity
Contraindications	Documented hypersensitivity; systemic infections and severe cytopenias
Interactions	Allopurinol may increase toxicity of azathioprine, and a dosage adjustment is necessary; azathioprine may reduce effects of warfarin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Nausea and vomiting, leukopenia, thrombocytopenia, anemia, infection, abnormal liver function tests may occur

Drug Name	Sulfasalazine (Azulfidine)
Description	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.
Adult Dose	1 g PO qd/qid; not to exceed 3 g/d
Pediatric Dose	<2 years: Do not administer >2 years: 40-60 mg/kg/d PO divided bid/tid Maintenance: 30 mg/kg/d PO in divided doses
Contraindications	Documented hypersensitivity to salicylates or sulfas; porphyria; intestinal or urinary tract obstructions
Interactions	Reduces digoxin concentrations; concurrent methenamine can result in crystalluria; inhibits metabolism of warfarin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal or hepatic function impairment, allergy, or aspirin-sensitive asthma, G-6-PD deficiency, blood dyscrasias

Drug Name	Methotrexate (Rheumatrex)
Description	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.
Adult Dose	In autoimmune conditions: 7.5-25 mg/wk PO/SC as single dose; folic acid supplementation is usually given concomitantly
Pediatric Dose	5-15 mg/m2/wk PO/SC as single dose
Contraindications	Liver or renal dysfunction, alcohol abuse, preexisting profound bone marrow depression, certain pulmonary diseases
Interactions	Oral tetracyclines and aminoglycosides reduce methotrexate absorption by 30-50%; antimalarials may reduce methotrexate levels; binding resins may reduce methotrexate levels; omeprazole and penicillins may increase methotrexate levels; etretinate increases risk of hepatotoxicity Cyclosporine reduces methotrexate excretion and may increase toxicity; trimethoprim/ sulfamethoxazole also inhibits folate metabolism, thus potentiating methotrexate toxicity
Pregnancy	X - Contraindicated in pregnancy
Precautions	Monitor CBC count, LFTs, BUN, and creatinine at regular intervals, usually every mo at the initiation of therapy; monitor for cough or shortness of breath for possibility of pneumonitis

Drug Name	Cyclophosphamide (Cytoxan, Neosar)
Description	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.
Adult Dose	0.5-2 mg/kg/d PO
Pediatric Dose	1-2.5 mg/kg/d PO
Contraindications	Documented hypersensitivity; suppressed bone marrow function; infections; prostatic hyperplasia; lower urinary tract obstruction; previous history of hemorrhagic cystitis
Interactions	Long-term high-dose phenobarbital therapy may increase metabolism to its active metabolite increasing toxicity; inhibits cholinesterase activity for up to 10 days after an intravenous dose which can potentiate the effect of succinylcholine chloride
Pregnancy	D - Unsafe in pregnancy
Precautions	Toxicities include nausea and vomiting, leukopenia, thrombocytopenia, anemia, infection, alopecia, hemorrhagic cystitis, infertility, teratogenicity, and risk of malignancy

Drug Name	Colchicine
Description	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.
Adult Dose	0.6-1.8 mg PO qd in divided doses
Pediatric Dose	Children: Not established Adolescents: Administer as in adults
Contraindications	Documented hypersensitivity; serious gastrointestinal, renal, hepatic, and cardiac disorders, blood dyscrasias
Interactions	Sympathomimetic agent toxicity and effect of CNS depressants are significantly increased with colchicine
Pregnancy	D - Unsafe in pregnancy
Precautions	Older patients, children, and lactation; may induce ileal vitamin B-12 malabsorption; can cause a peripheral neuritis, diarrhea, malaise, nausea, vomiting, alopecia, and dermatitis; monitor patients for cytopenias

Drug Name	Tacrolimus (Prograft, Protopic)
Description	Used to treat atopic dermatitis and for prophylaxis of renal and kidney transplant rejection.
Adult Dose	Atopic dermatitis: Apply thin layer of 0.03% or 0.1% ointment to affected areas bid Kidney transplant rejection prophylaxis: 0.2 mg/kg/d PO in 2 divided daily doses q12h Kidney transplant rejection prophylaxis: 0.03-0.05 mg/kg/d continuous IV infusion; convert to PO formulation as soon as possible Liver transplant rejection prophylaxis: 0.03-0.05 mg/kg/d continuous IV infusion; convert to PO formulation as soon as possible Liver transplant rejection prophylaxis: 0.1-0.15 mg/kg/d PO in 2 divided doses q12h
Pediatric Dose	Atopic dermatitis (ages 2-15 y): Apply thin layer of 0.03% ointment to affected areas bid Liver transplant rejection prophylaxis: 0.03-0.05 mg/kg/d continuous IV infusion Liver transplant rejection prophylaxis: 0.15-0.2 mg/kg/d PO in divided doses q12h
Contraindications	Documented hypersensitivity to tacrolimus products or hydrogenated castor oil (IV formulation)
Interactions	Caution with drugs associated with renal dysfunction, including aminoglycoside, amphotericin B, cisplatin, and others (can enhance nephrotoxicity); concentrations may be increased in presence of diltiazem, nicardipine, nifedipine, verapamil, clotrimazole, fluconazole, itraconazole, ketoconazole, clarithromycin, erythromycin, troleandomycin, cisapride, metoclopramide, bromocriptine, cimetidine, cyclosporine, danazol, methylprednisolone, and protease inhibitors; concentrations may decrease when administered with carbamazepine, phenobarbital, phenytoin, rifabutin, and rifampin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Shown to cross placenta and may cause neonatal hyperkalemia and renal dysfunction in pregnancy (ointment may be used during pregnancy only if benefits to mother outweigh risks to fetus) Renal insufficiency; monitor CBC count and urinalysis q1-2mo; toxicity is common, including pruritic and urticarial rash, nausea, dysgeusia, and stomatitis; can cause proteinuria and different forms of renal disease; can cause thrombocytopenia, neutropenia, and aplastic anemia; reports indicate that different autoimmune diseases have been triggered by this drug (eg, myasthenia gravis, inflammatory myopathies, Goodpasture syndrome)

Drug Category: Topical skin product

Agents such as imiquimod may induce mediators of immune processes.

FOLLOW-UP

Section 8 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

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

Deterrence/Prevention

• Early evaluation for prevention and treatment of joint and muscle contractures and deformities is important.
• Cases that involve children with severe facial deformities should be referred to a plastic surgeon early for prompt evaluation and consultation about possible treatment.

Complications

• Joint contractures, deformities, and severe limb atrophy can occur in linear scleroderma.
• • Severe atrophy of underlying muscle and bone also can occur.
  • Disabling pansclerotic morphea of childhood can include claw deformity of the hands.
  • Arthralgias, osteoporosis, flexion contractures, and other bone changes are frequent.
• A 1.5- to 7-cm leg length discrepancy can occur in 20% of patients with linear scleroderma.
• Psychosocial problems related to adjusting to deformities and disfiguration can occur.
• Loss of eyebrow or eyelashes, ptosis, pseudooculomotor palsy, uveitis, asymmetry of the tongue, and altered dentition and dental caries can occur in morphea en coup de sabre.
• Overt seizures may occur in Parry-Romberg syndrome.
• Aplastic anemia, thrombocytopenia, and hemolytic anemia have been reported in 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. If the chest wall is markedly involved, there may be difficulty in breathing due to constriction of the thorax.
• In patients with mediastinal and retroperitoneal fibrosis, complications are related to obstruction of vascular structures, bronchi, or ureters.
• Complications in Dupuytren contracture are related to progressive hand deformities.

Prognosis

• In general, localized and regional fibrosing disorders have 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 for a long time in about one-third of the patients.
• Linear lesions tend to persist longer than plaque lesions.
• Contractures may limit joint movements and lead to clawing of the hands.
• Facial hemiatrophy persists.
• Individuals with the severe inflammatory subtypes, en coup de sabre linear scleroderma, or Parry-Romberg disease can have severe functional limitations.
• In mediastinal and retroperitoneal fibrosis, the prognosis is related to the amount of irreversible obstruction.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Distinguish localized scleroderma from systemic sclerosis in early stages.

Special Concerns

• In children, lesions can have a major impact on growth and result in major facial or limb asymmetry, flexion contractures, and disability.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  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).
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Media type:  Photo

Media file 2:  This photograph shows generalized morphea on the trunk of a patient (reproduced with permission from Mayo Clinic Proceedings).
	View Full Size Image
Media type:  Photo

Media file 3:  CT scan of the abdomen showing the typical paraaortic mass of retroperitoneal fibrosis.
	View Full Size Image
Media type:  CT

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Dehen L, Roujeau JC, Cosnes A, Revuz J. Internal involvement in localized scleroderma. Medicine (Baltimore). Sep 1994;73(5):241-5. [Medline].
• Eguchi T, Harii K, Sugawara Y. Repair of a large "coup de sabre" with soft-tissue expansion and artificial bone graft. Ann Plast Surg. Feb 1999;42(2):207-10. [Medline].
• Falanga V, Medsger TA Jr, Reichlin M, Rodnan GP. Linear scleroderma. Clinical spectrum, prognosis, and laboratory abnormalities. Ann Intern Med. Jun 1986;104(6):849-57. [Medline].
• Ghersetich I, Teofoli P, Benci M, et al. Localized scleroderma. Clin Dermatol. Apr-Jun 1994;12(2):237-42. [Medline].
• Gilkeson GS, Allen NB. Retroperitoneal fibrosis. A true connective tissue disease. Rheum Dis Clin North Am. Feb 1996;22(1):23-38. [Medline].
• Jablonska S, Blaszczyk M. Sclerodermalike diseases. Clin Dermatol. Jul-Sep 1994;12(3):437-48. [Medline].
• Kerscher M, Volkenandt M, Gruss C, et al. Low-dose UVA phototherapy for treatment of localized scleroderma. J Am Acad Dermatol. Jan 1998;38(1):21-6. [Medline].
• Mancuso G, Berdondini RM. Localized scleroderma: response to occlusive treatment with tacrolimus ointment. Br J Dermatol. Jan 2005;152(1):180-2. [Medline].
• Mathisen DJ, Grillo HC. Clinical manifestation of mediastinal fibrosis and histoplasmosis. Ann Thorac Surg. Dec 1992;54(6):1053-7; discussion 1057-8. [Medline].
• Mizutani H, Yoshida T, Nouchi N, et al. Topical tocoretinate improved hypertrophic scar, skin sclerosis in systemic sclerosis and morphea. J Dermatol. Jan 1999;26(1):11-7. [Medline].
• Namazi MR. Imiquimod: a potential weapon against morphea and fibromatoses. J Drugs Dermatol. Jul-Aug 2004;3(4):362-3. [Medline].
• Peterson LS, Nelson AM, Su WP. Classification of morphea (localized scleroderma). Mayo Clin Proc. Nov 1995;70(11):1068-76. [Medline].
• Schachter RK. Localized scleroderma. Curr Opin Rheumatol. Dec 1989;1(4):505-11. [Medline].
• Schumacher HR. Multifocal fibrosclerosis. In: Cecil Textbook of Medicine. WB Saunders Co;2000:1561-62.
• Todd DJ, Askari A, Ektaish E. PUVA therapy for disabling pansclerotic morphoea of children. Br J Dermatol. Jan 1998;138(1):201-2. [Medline].
• Varga J, Kahari VM. Eosinophilia-myalgia syndrome, eosinophilic fasciitis, and related fibrosing disorders. Curr Opin Rheumatol. Nov 1997;9(6):562-70. [Medline].

Article Last Updated: Nov 7, 2006