UNC Morning Report

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Scleromyxedema

• UNC Morning Report
• December 16, 2009
• Christine Williams, MD

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SCLEROMYXEDEMA

• Also called
• lichen myxedematosus
• scleromyxedema of Groton
• papular mucinosis
• Epidemiology quite rare, largest case series 26
• Average age 55
• 31 Female to male ratio

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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

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SKIN FINDINGS Scleromyxedema
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SKIN FINDINGS Scleromyxedema
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Associated Organ Involvement

• Raynauds phenomenon
• Esophageal dysmotility
• Myopathy
• Pulmonary hypertension has been reported
• Neurologic symptoms
• Encephalopathy, seizures, coma and psychosis

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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

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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

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DIFFERENTIAL IMMUNOLOGIC

• Scleroderma
• Obliterative vasculopathy, extensive collagen
  deposition and fibrosis
• Eosinophilic fasciitis (Shulmans syndrome)
• GVHD
• Lichen sclerosus et atrophicus
• POEMS Syndrome
• Polyneuropathy, organomegaly, endocrinopathy,
  monoclonal gammopathy and skin changes
• SLE, dermatomyositis overlap syndromes

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DIFFERENTIAL METABOLIC/GENETIC

• Porphyria cutanea tarda
• Hypothyroidism (myxedema)
• Phenylketonuria
• Stiff skin syndrome
• congenital facial dystrophy
• Progeroid disorders
• Progeria, acrogeria

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DIFFERENTIAL DEPOSITION

• Systemic amyloidosis
• Nephrogenic systemic fibrosis
• Scleredema adultorum
• Lipodermatosclerosis

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DIFFERENTIAL TOXIC/OCCUPATIONAL

• Polyvinyl chloride
• Organic solvents
• Silica
• Epoxy resins
• Bleomycin
• Pentazocine
• Carbidopa
• Eosinophilia-myalgia sydnrome (L-tryptophan)
• Toxic-oil syndrome (aniline-denatured rapeseed
  oil)
• Post-radiation fibrosis

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SCLERODERMA

• 1-2100,000
• Ages 30-50, more common in women
• Diffuse cutaneous systemic sclerosis
• Limited cutaneous systemic sclerosis
• Calcinosis cutis
• Raynauds phenomenon
• Esophageal dysmotility
• Sclerodactyly
• Telangiectasia

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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

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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, macrovascular
  dz
• 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.

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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 peau
  dorange ? 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?, imatinib mesylate, PT,
  pain management

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Nephrogenic Systemic Fibrosis
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Eosinophilic Fasciitis

• Scleroderma-like painful skin lesions of
  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
• Synovitis and constitutional symptoms possible
• 21 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-myalgia sydrome, US
  89)
• Rx Corticosteroids, PT

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Eosinophilic Fasciitis
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SCLEREDEMA(Scleredema Adultorum/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
• Monclonal gammopathies type 2
• Multiple myeloma IgG, IgA, MGUS, Waldenstroms
• Poorly controlled DM type 3
• Treatment - treat underlying disease
• Immunosuppressants (steroids, MTX) w/o clear
  benefit
• PUVA therapy, UVA-1 treatment

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SCLEREDEMA
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Proposed approach to differential

• History for risk factors, exposure to gadolinium
• Raynauds phenomenon
• Skin distribution
• Presence of neurologic disease
• ANA
• SPEP
• Full-thickness skin biopsy

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Scleroderma Scleromyxedema Scleredema Eosin. Fasciitis NSF
Skin Thick, indurated Papular, waxy Indurated, doughy Indurated, woody Cobblestone, nodular plaques
Distribution Hands, face, chest Back spared Face, neck, arms, fingers Neck, back, face Extremities, trunk Hands/feet spared Extremities, trunk Face spared
Raynauds Almost All Rare No Rare Rare
Nailfold cap. Abnormal Normal Normal Normal Normal
ANA Positive (95) Rare Negative Rare Negative
Neurologic Rare Seizures, delirium, coma None Carpal tunnel Peripheral Neuropathy
Association Monoclonal gammopathy Infection, monoclonal ab, DM Morphea, cytopenias, malignancy Renal failure, transplant, gadolinium exposure
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REFERENCES

• Boin F, Hummers LK. Scleroderma-like fibrosing
  disorders. Rheum Dis Clin North Am. 2008
  Feb34(1)199-220 ix.
• Rey JB, Luria RB. Treatment of scleromyxedema and
  the dermatoneuro syndrome with intravenous
  immunoglobulin. J Am Acad Dermotol. 2009
  Jun60(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.