Understanding Scleromyxedema: Rare Skin Condition Overview

1. Scleromyxedema UNC Morning Report December 16, 2009 Christine Williams, MD

2. SCLEROMYXEDEMA • Also called • lichen myxedematosus • scleromyxedema of Groton • papular mucinosis • Epidemiology: quite rare, largest case series 26 • Average age 55 • 3:1 Female to male ratio

3. PHYSICAL FINDINGS: Scleromyxedema • Flesh colored to yellow/red, papular skin eruption • Indurated with a cobblestone feel • Distribution includes head, posterior auricular area, neck, arms and trunk • Midportion of back can be involved • NOT involved in scleroderma • Sclerodactyly can be present but papular

4. SKIN FINDINGS: Scleromyxedema

5. SKIN FINDINGS: Scleromyxedema

6. Associated Organ Involvement • Raynaud’s phenomenon • Esophageal dysmotility • Myopathy • Pulmonary hypertension has been reported • Neurologic symptoms • Encephalopathy, seizures, coma and psychosis

7. LABORATORY DATA: Scleromyxedema • Monoclonal gammopathy with lambda chains • Level of paraprotein does not decrease after effective treatment • Pathogenesis unclear • Mucinous deposition throughout the dermis • Thick collagen bundles • Increased fibroblast-like cells • Inflammatory infiltrate • Autoimmune markers typically negative

8. TREATMENT: Scleromyxedema • Variable immunosuppressants have been tried • IVIG 2g/kg monthly for 2-3 months then maintenance every 10-12 weeks • Melphalan • Cyclophosphamide • Cyclosporine • Thalidomide • Stem cell transplant has been used

9. DIFFERENTIAL: IMMUNOLOGIC • Scleroderma • Obliterative vasculopathy, extensive collagen deposition and fibrosis • Eosinophilic fasciitis (Shulman’s syndrome) • GVHD • Lichen sclerosus et atrophicus • POEMS Syndrome • Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes • SLE, dermatomyositis overlap syndromes

10. DIFFERENTIAL: METABOLIC/GENETIC • Porphyria cutanea tarda • Hypothyroidism (myxedema) • Phenylketonuria • Stiff skin syndrome • congenital facial dystrophy • Progeroid disorders • Progeria, acrogeria

11. DIFFERENTIAL: DEPOSITION • Systemic amyloidosis • Nephrogenic systemic fibrosis • Scleredema adultorum • Lipodermatosclerosis

12. DIFFERENTIAL: TOXIC/OCCUPATIONAL • Polyvinyl chloride • Organic solvents • Silica • Epoxy resins • Bleomycin • Pentazocine • Carbidopa • Eosinophilia-myalgiasydnrome (L-tryptophan) • Toxic-oil syndrome (aniline-denatured rapeseed oil) • Post-radiation fibrosis

13. SCLERODERMA • 1-2:100,000 • Ages 30-50, more common in women • Diffuse cutaneous systemic sclerosis • Limited cutaneous systemic sclerosis • Calcinosis cutis • Raynaud’s phenomenon • Esophageal dysmotility • Sclerodactyly • Telangiectasia

14. SCLERODERMA • Early in disease, arthralgias and soft tissue swelling may be more prominent • Heartburn/Dysphagia • DOE • Pulmonary HTN • Diarrhea w/malabsorption • Mucocutaneous telangiectasias • Digital infarctions • Hyperpigmentation • Calcinosis cutis • 10% do not have skin induration

15. SCLERODERMA: Autoantibodiess • ANA screening (95% +) • Anti-PM-Scl • Increased risk of myositis • Anti-Scl 70 – DNA topoisomerase I (dcSSc) • Increased risk of interstitial lung disease • Anti-centromere (lcSSc) • Anti-U3-RNP • Increased risk of Pulmonary HTN and myositis • Anti-RNA polymerase III • Anti-B2 glycoprotein I • Increased risk of thromboembolism, macrovasculardz • Specific 99% • Not sensitive 20-50% • High titers of RF, anti-CCP, anti-U1 RNP, anti-dsDNA or anti-Smith uncommon. ANCA not associated with systemic sclerosis.

16. Nephrogenic Systemic Fibrosis • History of renal failure and HD • Gadolinium exposure , high epo doses are associated • Rapidly developing, days to weeks • Confluent fibrotic skin induration ‘peaud’orange’  cobblestone • Nodular plaques which become woody • Tender, pruritic, burning • Brawny hyperpigmentation • Flexion contractures • Stocking/glove distribution, face usually spared • Muscles, myocardium, lungs, kidneys and testes • Fibroblast proliferation, thick collagen bundles and mucin deposition (very similar) but can extend into adipose and muscle layers • MRI – increased T1 signal in muscles, fascial and muscular edema • Rx-sodium thiosulfate?, imatinibmesylate, PT, pain management

17. Nephrogenic Systemic Fibrosis

18. Eosinophilic Fasciitis • Scleroderma-like painful skin lesionsof extremities (forearms/calves) • Hands and face usually spared • Hypergammaglobulinemia (polyclonal) • Eosinophilia • Dermal/hypodermal sclerosis w/fibrotic thickening of subcutaneous adipose septa, superficial fascia and perimysium • Epidermis spared • Flexion contractures and peripheral nerve compression can complicate • Synovitisand constitutional symptoms possible • 2:1 male: female ratio • Preceded by vigorous exercise or trauma in 50% • 10-15% have underlying hematologic d/o or malignancy • Associated with spirochetes • Similar to symptoms from • rapeseed oil (Toxic oil sydrome, Spain ‘81) • L-tryptophan (eosinophilia-myalgiasydrome, US ‘89) • Rx: Corticosteroids, PT

19. Eosinophilic Fasciitis

20. SCLEREDEMA(ScleredemaAdultorum/Buschke) • Deposition of collagen and mucin causing thickening of the dermis • Non-pitting, doughy or woody induration • Neck, back, interscapular region, face, chest • Associated with • Post-infectious (strep), occurs in children also [type 1] • Monclonalgammopathies [type 2] • Multiple myeloma IgG, IgA, MGUS, Waldenstrom’s • Poorly controlled DM [type 3] • Treatment - treat underlying disease • Immunosuppressants (steroids, MTX) w/o clear benefit • PUVA therapy, UVA-1 treatment

21. SCLEREDEMA

22. Proposed approach to differential • History for risk factors, exposure to gadolinium • Raynaud’s phenomenon • Skin distribution • Presence of neurologic disease • ANA • SPEP • Full-thickness skin biopsy

24. REFERENCES • Boin F, Hummers LK. Scleroderma-like fibrosing disorders. Rheum Dis Clin North Am. 2008 Feb;34(1):199-220; ix. • Rey JB, Luria RB. Treatment of scleromyxedema and the dermatoneuro syndrome with intravenous immunoglobulin. J Am Acad Dermotol. 2009 Jun;60(6):1027-41. Epub 2009 Feb 26. • Varge, J. Diagnosis and differential diagnosis of systemic sclerosis (scleroderma) in adults. UpToDate. Online. (utdol.com) Accessed 14 December 2009.