What are the management options for sclerosis?

Management of Sclerosis

Critical First Step: Clarify the Diagnosis

The term "sclerosis" encompasses multiple distinct diseases requiring completely different management approaches—you must first determine whether this is systemic sclerosis (scleroderma), multiple sclerosis, or lichen sclerosus, as treatments are not interchangeable. 1

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If This Is SYSTEMIC SCLEROSIS (Scleroderma):

Immediate Referral and Early Intervention

Refer immediately to a specialized center if early diffuse cutaneous disease or interstitial lung disease is suspected, as early immunosuppression can prevent irreversible fibrotic damage. 2, 3

• Inflammation is reversible if treated early but transforms into permanent fibrosis if delayed 3
• Over 95% of patients present with Raynaud's phenomenon as the first manifestation 2, 3
• Quantify skin involvement using the modified Rodnan skin score (0-51 scale) 1, 2

Mandatory Visceral Screening

Screen systematically for life-threatening organ involvement at diagnosis and regularly thereafter: 2, 3

• Interstitial lung disease: Chest radiograph, pulmonary function tests (especially DLCO), and high-resolution CT if indicated 2, 3
• Pulmonary arterial hypertension: Screen with DLCO measurement; decreased DLCO significantly increases PAH risk 2, 3
• Renal crisis: Monitor blood pressure and renal function closely, especially in early diffuse cutaneous disease 2, 3
• Gastrointestinal involvement: Assess for gastroesophageal reflux (present in ~90% of patients) and malnutrition (the leading GI-related cause of death) 2, 3

Organ-Specific Treatment Algorithm

For Early Diffuse Cutaneous Disease:

• First-line: Mycophenolate mofetil 1, 2, 3, 4
• Second-line options: Rituximab, tocilizumab, or methotrexate 1, 4
• For rapidly progressive disease with high mortality risk: Consider autologous hematopoietic stem cell transplantation 1, 4

For Interstitial Lung Disease:

• First-line: Mycophenolate mofetil 1, 2, 3, 4
• For progressive pulmonary fibrosis: Add nintedanib as anti-fibrotic therapy 1, 4
• Alternative immunosuppressives: Cyclophosphamide, rituximab, or tocilizumab 1, 4
• Ensure pneumococcal, influenza, and COVID-19 vaccinations are current before starting immunosuppression 3, 4
• Provide supplemental oxygen if hypoxia is present 4

For Pulmonary Arterial Hypertension:

• Initial combination therapy is mandatory: Phosphodiesterase-5 inhibitor PLUS endothelin receptor antagonist 1, 2, 3, 4
• For pulmonary hypertension secondary to ILD: Consider inhaled treprostinil 4

For Raynaud's Phenomenon:

• First-line: Dihydropyridine calcium channel blockers 1, 2, 3, 4
• Second-line: Phosphodiesterase-5 inhibitors 1, 4
• Third-line: Endothelin receptor antagonists 1, 4
• Alternative: Fluoxetine may be considered 1, 4
• Non-pharmacologic: Advise use of gloves, heating devices, avoid cold exposure and direct contact with cold surfaces 1

For Digital Ulcers:

• Prevention hierarchy: Calcium channel blockers → PDE-5 inhibitors → endothelin receptor antagonists 4

For Scleroderma Renal Crisis:

• Initiate high-dose ACE inhibitors immediately 2, 3
• Critical warning: Glucocorticoid doses ≥15 mg/day significantly increase renal crisis risk 2, 3

For Gastroesophageal Reflux:

• First-line: Proton pump inhibitors, prescribed aggressively 2, 3

Essential Non-Pharmacologic Management

Patient education and self-management support improve hand function, oral outcomes, quality of life, and ability to perform daily activities. 1, 3

• Orofacial exercises for microstomia 1
• Hand exercises for hand function 1
• Aerobic and resistance exercise for physical capacity 1
• Manual lymph drainage for puffy hands 1

Critical Pitfalls to Avoid

• Never delay immunosuppression—early treatment prevents irreversible damage 2, 3
• Avoid glucocorticoids ≥15 mg/day—dramatically increases renal crisis risk 2, 3
• Screen for malignancy in elderly patients with rapidly progressive diffuse disease, weight loss, and anti-RNA polymerase III antibodies 2, 3
• Assess for depression and osteoporosis—both are common comorbidities requiring specific management 2, 3

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If This Is MULTIPLE SCLEROSIS:

Disease-Modifying Therapy Selection

High-efficacy disease-modifying therapies initiated early provide superior outcomes compared to escalation approaches. 5

• Preferred high-efficacy agents include natalizumab and fingolimod based on current practice patterns 5
• Moderate-efficacy option: Dimethyl fumarate 5
• The evidence increasingly favors early aggressive treatment over traditional escalation strategies 5

Relapse Management

• Intravenous high-dose corticosteroids are strongly preferred for acute relapses 5
• Treat even nondisabling relapses (e.g., mild sensory symptoms) according to majority practice 5

Symptom Management

Address common symptoms systematically: 6

• Spasticity, fatigue, sexual dysfunction, bladder dysfunction, pain, and cognitive dysfunction require individualized multimodal approaches 6
• Depression, bowel dysfunction, paroxysmal symptoms, and weakness also need attention 6
• Combine patient education, physical modalities, occupational therapy, and pharmacologic interventions 6

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If This Is LICHEN SCLEROSUS:

Primary Treatment

Topical ultrapotent corticosteroids are the mainstay of treatment for uncomplicated lichen sclerosus. 1

• "Complicated" lichen sclerosus with squamous cell hyperplasia responds more poorly to corticosteroids 1
• Autoimmune mechanisms are implicated in pathogenesis 1
• Two peak incidence periods: prepubertal girls and postmenopausal women 1

Monitoring

• Regular follow-up is essential given the chronic nature and potential complications 1