Scleroderma

para>Uncommon >75 years of age é á
Pediatric Considerations

Rare in this age group

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Pregnancy Considerations

Safe and healthy pregnancies are common and possible despite higher frequency of premature births.
High-risk management must be standard care to avoid complications, specifically renal crisis.
Diffuse scleroderma causes greater risk for developing serious cardiopulmonary and renal problems. Pregnancy should be delayed until disease stabilizes.

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EPIDEMIOLOGY

Incidence

In the United States: 1 to 2/100,000/year
Predominant age
- Young adult (16 to 40 years); middle-aged (40 to 75 years), peak onset 30 to 50 years
- Symptoms usually appear in the 3rd to 5th decades.
Predominant sex: female > male (4:1)

Prevalence
In the United States: 1 to 25/100,000 é á

ETIOLOGY AND PATHOPHYSIOLOGY

Pathophysiology involves both a vascular component and a fibrotic component. Both occur simultaneously. The inciting event is unknown, but there is an increase in certain cytokines after endothelial cell activation that are profibrotic (TGF- Ä ▓ and PDGF). é á

Unknown
Possible alterations in immune response
Possibly some association with exposure to quartz mining, quarrying, vinyl chloride, hydrocarbons, toxin exposure
Treatment with bleomycin has caused a scleroderma-like syndrome, as has exposure to rapeseed oil.

Genetics
Familial clustering is rare, but has been seen. é á

RISK FACTORS

Unknown é á

DIAGNOSIS

HISTORY

Raynaud phenomenon is generally the presenting complaint (differentiated from Raynaud disease, generally affecting younger individuals and without digital ulcers).
Skin thickening, "puffy hands, " Ł pruritus, and gastroesophageal reflux disease (GERD) are often noted early in the disease process.

PHYSICAL EXAM

Skin
- Digital ulcerations
- Digital pitting
- Tightness, swelling, thickening of digits
- Hyperpigmentation/hypopigmentation
- Narrowed oral aperture
- SC calcinosis
Peripheral vascular system
- Telangiectasia
Joints, tendons, and bones
- Flexion contractures
- Friction rub on tendon movement
- Hand swelling
- Joint stiffness
- Polyarthralgia
- Sclerodactyly
Muscle
- Proximal muscle weakness
GI tract
- Dysphagia
- Esophageal reflux due to dysmotility (most common systemic sign in diffuse disease)
- Malabsorptive diarrhea
- Nausea and vomiting
- Weight loss
- Xerostomia
Kidney
- Hypertension
- May develop scleroderma renal crisis: acute renal failure (ARF)
Pulmonary
- Dry crackles at lung bases
- Dyspnea
Nervous system
- Peripheral neuropathy
- Trigeminal neuropathy
Cardiac (progressive disease)
- Conduction abnormalities
- Cardiomyopathy
- Pericarditis
- Secondary cor pulmonale

DIFFERENTIAL DIAGNOSIS

Mixed connective tissue disease/overlap syndromes
Scleredema
Nephrogenic systemic fibrosis
Toxic oil syndrome (Madrid, 1981, affecting 20,000 people)
Eosinophilia " ômyalgia syndrome
Diffuse fasciitis with eosinophilia
Scleredema of Buschke

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Nail fold capillary microscopy " ödrop out is most significant finding
CBC
Creatinine
Urinalysis (albuminuria, microscopic hematuria)
Antinuclear antibodies (ANA): positive in >90% of patients
Anti " ôScl-70 (anti-topoisomerase [ATA]) antibody is highly specific for systemic disease and confers a higher risk of interstitial lung disease (ILD).
Anticentromere antibody usually associated with CREST variant
Chest radiograph
- Diffuse reticular pattern
- Bilateral basilar pulmonary fibrosis
Hand radiograph
- Soft tissue atrophy and acro-osteolysis
- Can see overlap syndromes such as rheumatoid arthritis
- SC calcinosis

Follow-Up Tests & Special Considerations

Pulmonary function tests (PFTs)
- Decreased maximum breathing capacity
- Increased residual volume
- Diffusion defect
Antibodies to U3-RNP " öhigher risk for scleroderma-associated pulmonary hypertension
Anti " ôPM-Scl antibodies (for myositis) (2)[B]
Anti-RNA polymerase III " öhigher risk for diffuse cutaneous involvement and renal crisis (3)[A]
ECG (low voltage): possible nonspecific abnormalities, arrhythmia, and conduction defects
Echocardiography: pulmonary hypertension or cardiomyopathy
Nail fold capillary loop abnormalities
Upper GI
- Distal esophageal dilatation
- Atonic esophagus
- Esophageal dysmotility
- Duodenal diverticula
Barium enema
- Colonic diverticula
- Megacolon
High-resolution CT scan for detecting alveolitis, which has a ground-glass appearance or fibrosis predominant in bilateral lower lobes

Diagnostic Procedures/Other

Skin biopsy
- Compact collagen fibers in the reticular dermis and hyalinization and fibrosis of arterioles
- Thinning of epidermis, with loss of rete pegs, and atrophy of dermal appendages
- Accumulation of mononuclear cells is also seen.
Right-sided heart catheterization: Pulmonary hypertension is an ominous prognostic feature.

Test Interpretation

Skin
- Edema, fibrosis, or atrophy (late stage)
- Lymphocytic infiltrate around sweat glands
- Loss of capillaries
- Endothelial proliferation
- Hair follicle atrophy
Synovium
- Pannus formation
- Fibrin deposits in tendons
Kidney
- Small kidneys
- Intimal proliferation in interlobular arteries
Heart
- Endocardial thickening
- Myocardial interstitial fibrosis
- Ischemic band necrosis
- Enlarged heart
- Cardiac hypertrophy
- Pulmonary hypertension
Lung
- Interstitial pneumonitis
- Cyst formation
- Interstitial fibrosis
- Bronchiectasis
Esophagus
- Esophageal atrophy
- Fibrosis

TREATMENT

GENERAL MEASURES

Treatment is symptomatic and supportive.
Esophageal dilation may be used for strictures.
Avoid cold; dress appropriately in layers for the weather; be wary of air conditioning.
Avoid smoking (crucial).
Avoid finger sticks (e.g., blood tests).
Elevate the head of the bed during sleep to help relieve GI symptoms.
Use softening lotions, ointments, and bath oils to help prevent dryness and cracking of skin.
Dialysis may be necessary in renal crisis.

MEDICATION

First Line

ACE inhibitors (ACEIs): for preservation of renal blood flow and for treatment of hypertensive renal crisis
Corticosteroids: for disabling myositis, pulmonary alveolitis, or mixed connective tissue disease (not recommended in high doses due to increased incidence of renal failure)
NSAIDs: for joint or tendon symptoms. Caution with long-term concurrent use with ACEIs (potential renal complications)
Antibiotics: for secondary infections in bowel and active skin infections
Antacids, proton pump inhibitors: for gastric reflux
Metoclopramide: for intestinal dysfunction
Hydrophilic skin ointments: for skin therapy
Topical clindamycin, erythromycin, or silver sulfadiazine: for prevention of recurrent infectious cutaneous ulcers
Consider immunosuppressives for treatment of life-threatening or potentially crippling scleroderma or interstitial pneumonitis such as cyclophosphamide for ILD (4)[B].
Nitrates and dihydropyridine calcium-channel blockers for Raynaud phenomenon
Avoidance of caffeine, nicotine, and sympathomimetics may ease Raynaud symptoms.
PDE-5 antagonists (e.g., sildenafil), prostanoids, and endothelin-1 antagonists are changing the management of pulmonary hypertension (5).
Alveolitis: immunosuppressants and alkylating agents (e.g., cyclophosphamide)

ADDITIONAL THERAPIES

Anti " ôTNF-α therapy: Preliminary suggestion is that these may reduce joint symptoms and disability in inflammatory arthritis, but small sample sizes and observational biases lend to the need for further well-designed, adequately powered, longitudinal clinical trials.
Physical therapy to maintain function and promote strength
Heat therapy to relieve joint stiffness

SURGERY/OTHER PROCEDURES

Some success with gastroplasty for correction of GERD
Limited role for sympathectomy for Raynaud phenomenon
Lung transplantation for pulmonary hypertension and ILD

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

Monitor every 3 to 6 months for end-organ and skin involvement and medications. Provide encouragement.
Echocardiology and PFTs yearly

DIET

Drink plenty of fluids with meals. é á

PATIENT EDUCATION

Stay as active as possible, but avoid fatigue.
Printed patient information available from the Scleroderma Federation, 1725 York Avenue, No. 29F, New York, NY 10128; (212) 427-7040
Advise the patient to report any abnormal bruising or nonhealing abrasions.
Assist the patient about smoking cessation, if needed.

PROGNOSIS

Possible improvement but incurable
Prognosis is poor if cardiac, pulmonary, or renal manifestations present early.

COMPLICATIONS

Renal failure
Respiratory failure
Flexion contractures
Disability
Esophageal dysmotility
Reflux esophagitis
Arrhythmia
Megacolon
Pneumatosis intestinalis
Obstructive bowel
Cardiomyopathy
Pulmonary hypertension
Possible association with lung and other cancers
Death

REFERENCES

11 van den Hoogen é áF, Khanna é áD, Fransen é áJ, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737 " ô2747.22 D 'Aoust é áJ, Hudson é áM, Tatibouet é áS, et al. Clinical and serologic correlates of anti-PM/Scl antibodies in systemic sclerosis: a multicenter study of 763 patients. Arthritis Rheumatol. 2014;66(6):1608 " ô1615.33 Sobanski é áV, Dauchet é áL, Lef â Ęvre é áG, et al. Prevalence of anti-RNA polymerase III antibodies in systemic sclerosis: new data from a French cohort and a systematic review and meta-analysis. Arthritis Rheumatol. 2014;66(2):407 " ô417.44 Roth é áMD, Tseng é áCH, Clements é áPJ, et al. Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis Rheum. 2011;63(9):2797 " ô2808.55 Volkmann é áER, Saggar é áR, Khanna é áD, et al. Improved transplant-free survival in patients with systemic sclerosis-associated pulmonary hypertension and interstitial lung disease. Arthritis Rheumatol. 2014:66(7):1900 " ô1908.

ADDITIONAL READING

Herrick é áAL. Contemporary management of Raynaud 's phenomenon and digits ischaemic complications. Curr Opin Rheumatol. 2011;23(6):555.
Kowal-Bielecka é áO, Landewe é áR, Avouac é áJ, et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009;68(5):620 " ô628.
Phumethum é áV, Jamal é áS, Johnson é áSR. Biologic therapy for systemic sclerosis: a systematic review. J Rheumatol. 2011;38(2):289 " ô296.
Steen é áVD. Pregnancy in scleroderma. Rheum Dis Clin North Am. 2007;33(2):345 " ô358, vii.
Valerio é áCJ, Schreiber é áBE, Handler é áCE, et al. Borderline mean pulmonary artery pressure in patients with systemic sclerosis. Arthritis Rheum. 2013;65(4):1074 " ô1084.

CODES

ICD10

M34.9 Systemic sclerosis, unspecified
M34.1 CR(E)ST syndrome
L94.0 Localized scleroderma [morphea]
L94.1 Linear scleroderma
M34.89 Other systemic sclerosis
M34.83 Systemic sclerosis with polyneuropathy
M34.81 Systemic sclerosis with lung involvement
M34.0 Progressive systemic sclerosis
M34.82 Systemic sclerosis with myopathy

ICD9

710.1 Systemic sclerosis
517.8 Lung involvement in other diseases classified elsewhere

SNOMED

89155008 systemic sclerosis (disorder)
62382002 Calcinosis, Raynauds phenomenon, sclerodactyly, and telangiectasia syndrome (disorder)
201048007 Localized morphea (disorder)
22784002 Linear scleroderma (disorder)
196133001 Lung disease with systemic sclerosis (disorder)
299276009 Limited systemic sclerosis (disorder)
128460000 systemic sclerosis, diffuse (disorder)
7513007 Generalized morphea
236502006 Renal involvement in scleroderma

CLINICAL PEARLS

Raynaud phenomenon is frequently the initial complaint.
Skin thickening, "puffy hands, " Ł and GERD are often noted early in disease.
Patients must be followed proactively for development of pulmonary hypertension or ILD.

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