eMedicine Specialties > Rheumatology > Soft Tissue and Regional Rheumatic Disease
Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis: Treatment & Medication
Updated: Dec 3, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
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.
- 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, 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 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.
- 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.1
- 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 are usually 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.2 Imiquimod has also been suggested as a potential treatment for morphea and fibromatoses, but more studies are needed.3
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
- 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
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.4 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.
Antimalarials
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.
Adult
200-400 mg PO qd
Pediatric
6-7 mg/kg PO qd or divided bid; not to exceed 400 mg/d
Hydroxychloroquine may increase levels of digoxin and reduce levels of praziquantel
Documented hypersensitivity; retinal or visual field changes
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Requires careful ophthalmologic screening at baseline and q6-12mo to identify early retinal damage; psoriasis, porphyria, hepatic dysfunction, G-6-PD deficiency
Corticosteroids
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.
Adult
5-60 mg/d PO, depending on severity of symptoms; taper as manifestations resolve
Pediatric
0.5-2 mg/kg/d PO; taper as manifestations resolve
May cause water and salt retention; exacerbates hypertension increasing requirement for antihypertensive drugs in hypertensive patients; may aggravate hyperglycemia increasing requirement or hypoglycemic agents in diabetic patients; metabolism may be increased by drugs that induce hepatic microsomal enzymes requirements including phenytoin, phenobarbital, carbamazepine and rifampin, thus increasing the corticosteroid requirements
Documented hypersensitivity; severe bacterial, viral, or fungal infections; active peptic ulcer disease; diabetes mellitus
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Toxicities include weight gain, dyspepsia, mood changes, infection, peptic ulcer disease, hypertension, diabetes mellitus, osteoporosis, avascular necrosis, cataracts, glaucoma, myopathy and skin changes; growth retardation in children; abrupt discontinuation may result in adrenal crisis
Triamcinolone (Aristocort)
Can be helpful in inhibiting inflammation and fibrosis in localized fibrosing conditions. Repeated administrations might be necessary.
Adult
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
Administer as in adults
None reported
Documented hypersensitivity; fungal, viral, and bacterial skin infections
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
A percentage of topical drug might be absorbed systemically; if application is repeated, there may be some systemic effects of the corticosteroids
Immunosuppressives/disease-modifying antirheumatic drugs
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.
Adult
125-250 mg/d PO, increase 250 mg q2-3mo prn, not to exceed 1 g/d PO
Medication must be taken in morning, with an empty stomach; wait at least 2 h before ingesting any food
Pediatric
20-30 mg/kg/d PO divided qid
Antacids (magnesium-aluminum hydroxides) reduce bioavailability; may reduce digoxin concentrations; oral iron substantially reduces plasma penicillamine concentration, with reduced therapeutic response
Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution with concomitant use with other nephrotoxic drugs or administration of drugs or other substances that inhibit or induce CYP3A enzyme systems (systemic formulations); do not use simultaneously with cyclosporine (systemic formulations); hyperkalemia may develop; do not use potassium-sparing diuretics during therapy (systemic formulations); increases risk of lymphoma and other malignancies; increases risk of varicella-zoster virus infection, herpes simplex virus infection, or eczema herpeticum (topical); insulin-dependent posttransplant diabetes mellitus may develop (systemic formulations); limited data with pediatric kidney transplantation patients (systemic formulations)
May cause hypertension, myocardial hypertrophy (systemic formulations); minimize or avoid natural or artificial sunlight exposure (topical); neurotoxicity and nephrotoxicity may develop (systemic formulations); not recommended in patients with Netherton syndrome (topical); risk of anaphylactic reaction (injection); susceptibility to infection; vaccinations may be less effective; use of live vaccines should be avoided during therapy
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.
Adult
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
Administer as in adults
Allopurinol may increase toxicity of azathioprine, and a dosage adjustment is necessary; azathioprine may reduce effects of warfarin
Documented hypersensitivity; systemic infections and severe cytopenias
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Nausea and vomiting, leukopenia, thrombocytopenia, anemia, infection, abnormal liver function tests may occur
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.
Adult
1 g PO qd/qid; not to exceed 3 g/d
Pediatric
<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
Reduces digoxin concentrations; concurrent methenamine can result in crystalluria; inhibits metabolism of warfarin
Documented hypersensitivity to salicylates or sulfas; porphyria; intestinal or urinary tract obstructions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or hepatic function impairment, allergy, or aspirin-sensitive asthma, G-6-PD deficiency, blood dyscrasias
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.
Adult
In autoimmune conditions: 7.5-25 mg/wk PO/SC as single dose; folic acid supplementation is usually given concomitantly
Pediatric
5-15 mg/m2/wk PO/SC as single dose
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
Liver or renal dysfunction, alcohol abuse, preexisting profound bone marrow depression, certain pulmonary diseases
Pregnancy
X - Contraindicated; benefit does not outweigh risk
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
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.
Adult
0.5-2 mg/kg/d PO
Pediatric
1-2.5 mg/kg/d PO
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
Documented hypersensitivity; suppressed bone marrow function; infections; prostatic hyperplasia; lower urinary tract obstruction; previous history of hemorrhagic cystitis
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Toxicities include nausea and vomiting, leukopenia, thrombocytopenia, anemia, infection, alopecia, hemorrhagic cystitis, infertility, teratogenicity, and risk of malignancy
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.
Adult
0.6-1.8 mg PO qd in divided doses
Pediatric
Children: Not established
Adolescents: Administer as in adults
Sympathomimetic agent toxicity and effect of CNS depressants are significantly increased with colchicine
Documented hypersensitivity; serious gastrointestinal, renal, hepatic, and cardiac disorders, blood dyscrasias
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Tacrolimus (Prograft, Protopic)
Used to treat atopic dermatitis and for prophylaxis of renal and kidney transplant rejection.
Adult
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 divided 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 divided q12h
Pediatric
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 divided q12h
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
Documented hypersensitivity to tacrolimus products or hydrogenated castor oil (IV formulation)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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)
Topical Skin Product
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.
Adult
Actinic keratosis: Apply 5% cream to defined treatment area 2 times/wk hs for 16 wk; leave on skin for 8 h
Superficial basal cell carcinoma: Apply 5% cream to defined treatment area 5 times/wk hs for 6 wk; leave on skin for 8 h
Venereal warts: Apply 5% cream to affected area hs for 3 times/wk for up to 16 wk; leave on skin for 6-10 h
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Has not been evaluated for treatment of urethral, intravaginal, cervical, rectal, or intra-anal human papillomavirus disease; pediatric patients (safety and efficacy in patients <18 y have not been studied); avoid eye contact with topical product; if severe local skin reactions occur, the cream should be removed by washing the treatment area with soap and water; treatment can be resumed after the reaction has subsided; topical administration is not recommended until genital/perianal tissue is healed from any previous drug or surgical treatment; inflammatory conditions of the skin; may weaken condoms and vaginal diaphragms; thus, concurrent use is not recommended; safety and efficacy not established for basal cell nevus syndrome or xeroderma pigmentosum
More on Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis |
| Overview: Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis |
| Differential Diagnoses & Workup: Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis |
 Treatment & Medication: Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis |
| Follow-up: Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis |
| Multimedia: Localized Fibrosing Disorders - Linear Scleroderma, Morphea, and Regional Fibrosis |
| References |
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References
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Further Reading
Keywords
localized fibrosing disorders, linear scleroderma, morphea, regional fibrosis, localized scleroderma, systemic sclerosis, generalized morphea, en coup de sabre, retroperitoneal fibrosis, mediastinal fibrosis, Dupuytren contracture, morphea en plaque, plaque morphea, guttate morphea, keloid morphea, lichen sclerosus et atrophicus, atrophoderma of Pasini and Pierini, bullous morphea, deep morphea, subcutaneous morphea, morphea profunda, disabling pansclerotic morphea of childhood, eosinophilic fasciitis
