Cutaneous Manifestations of Internal Disease

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Cutaneous Manifestations of Internal Disease

• Adam O. Goldstein, MD, MPH
• Associate Professor
• Family Medicine
• University of North Carolina
• at Chapel Hill
• aog_at_med.unc.edu

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Cutaneous Manifestations of Internal Disease

• Objectives Recognize and evaluate patients with
  
• I. Vasculitis
• II. Rheumatologic disease
• III. Hypersensitivity syndromes
• IV. Pruritus

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I. Vasculitis

• Definition Inflammation of the vessel wall by
  immune complex deposition
• type of inflammatory cell (neutrophil,
  lymphocyte, histiocyte)
• size of vessel (venule, arteriole, artery or
  vein)

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Large/medium Vessel Vasculitis

• Clinical Presentation
• livedo reticularis
• subcutaneous nodules (malleoli/post calf)
• papulonecrotic lesions
• digital infarctions
• ulcers
• ecchymosis

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Differential Diagnosis

• Polyarteritis nodosa
• Wegeners Granulomatosis
• Churg-Strauss Syndrome

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Small Vessel Vasculitis

• Morphology
• palpable purpura
• urticaria
• hemorrhagic pustules
• nodules, bullae or ulcers
• Features
• fever, malaise, myalgia,
• arthralgia, lower ext. edema

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Differential Diagnosis/ Etiologies

• Infections Hepatitis B/C, acute Strep, viral URI
  
• ANCA
• Henoch-Schonlein Purpura
• Connective Tissue Disease
• Neoplasms

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Differential Dx Etiologies

• Cryoglobulinemia
• Hypersensitivity
• Medications
• penicillin, thiazides, aspirin, phenothiazines,
  sulfonamides, iodides
• Unknown

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Schambergs Disease

• frequently confused for vasculitis but benign
• progresssive pigmented purpuric dermatosis
• nonpalpable, brown staining
• petechiae/cayenne pepper-like
• no necrosis of vessels
• often lower extremities

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Small Vessel Vasculitis Signs/Symptoms

• Renal-mild to severe
• Peripheral neuropathy
• GI -abd.pain,N/V,diarrhea,melena
• Pulmonary-hemoptysis, cough, SOB, CXR only
• Joint
• Heart-arrthymia/CHF

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Small vessel vasculitis

• Perform a skin biopsy -routine and DIF from a
  palpable purpuric papule 24 hours old.
• Obtain an esr, cbc, u/a, liver/renal functions.

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Scenario 1-

• Skin biopsy results are conclusive
• In addition to vasculitis of the dermal vessels
  on routine histology, IgA deposition is noted in
  and around the vessels on the 4 mm punch specimen
  sent for DIF. The diagnosis is Henoch Schonelin
  Purpura.

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Scenario 2-

• Skin biopsy results are nonspecific
• Vasculitis is seen in the dermal vessels. RF,
  ANA, anti ds-DNA, Ro and La, complement and
  cyroglobulin levels, ANCA, SPEP, UPEP, CXR

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Scenario 3-

• Skin biopsy results are pending and patient is
  seriously ill
• combine entire work up while for waiting for the
  results of the skin biopsy.

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Patient Evaluation

• Identify and confirm source of offending antigen
  (drug/infection)
• throat culture/ASO titer
• ESR/CBC w/plt
• Creatinine
• U/A
• ANA

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Patient Evaluation (contd)

• SPEP/IEP
• Hepatitis B/C screening
• CH50
• Cryoglobulins
• Rheumatoid Factor

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Patient Evaluation (contd)

• Skin biopsy from new lesions (
• lumph predominate -CTD/ eos-Churg-Strauss
• Immunofluorescent studies if concerned about
  HSP(IgA)
• special media required
• CXR

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Small Vessel Vasculitis-Treatment

• Removal of offending etiology
• Symptomatic relief
• Prednisone 40-60 mg/day x 2-3 weeks
• Colchicine 0.6 mg bid for 7-10 days then taper
• Azathioprine/Dapsone

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Rheumatologic Diseases

• Lupus erythematosus
• Dermatomyositis
• Scleroderma
• Sjogrens Syndrome

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Systemic lupus erythematosus (SLE)

• chronic inflammatory disease of unknown cause
  skin, joints, kidneys, lungs, nervous system,
  serous membranes and/or other organs of the body.

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Lupus Erythematosus

• acute SLE/Bullous LE
• subacute SCLE/Neonatal/Drug-induced
• chronic discoid/ panniculitis

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Diagnosis of SLE

• 4/11ARA criteria are cutaneous
• 50 present w/skin finding
• 85 have skin findings at some point

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Specific findings

• discoid
• malar rash
• photosensitivity
• oral ulcers

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Nonspecific findings

• vasculitis
• urticarial vasculitis
• alopecia
• calcinosis cutis
• rhematoid nodules
• Raynauds

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Discoid LE

• distribution sun-exposed
• face and scalp
• papules, plaques
• erythema, pigmentary alteration, scarring,
  follicular plugging

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Discoid LE Ddx

• tinea facei/capitis
• scarring alopecia
• cicatricial pemphigoid
• hypertrophic lichen planus
• actinic keratoses

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Discoid LE Dx

• biopsy
• ANA
• CBC w/diff esr, BUN/Cr/u/a

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SLE

• malar rash
• erythematous macules/patches/plaques
• butterfly distribution
• photo induced
• asymptomatic
• NLF sparing
• 90 arthritis

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Lupus Profundus

• 3 w/ chronic cutaneous lupus
• More frequent in women
• Upper arms, shoulders, face, and buttocks
• Often trauma related
• Dx-biopsy

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SLE Ddx

• Rosacea
• IP/pustules/telang
• other triggers
• stinging/burning
• common

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SLE Ddx

• seborrhea
• paranasal scaling
• look for scalp/eyebrow involvement

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SLE Ddx

• Contact dermatitis
• pruritic, well-demarcated
• look for other sites

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SLE Dx

• ANA
• cbc/esr/cr/bun/u/a
• /- biopsy if other unclear

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SLE Lab Dx

• ANA 95-8
• DS DNA 40
• ENA 30
• RNP/Sm
• SSA/Ro 25

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Photosensitivity

• UVA and UVB
• r/o drug photosensitivity
• same as malar for w/u

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Oral Ulcers

• ddx lichen planus/aphthae/pemphigus
• w/u same as malar rash

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SCLE

• 10 of all SLE
• older
• milder disease

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SCLE

• face/neck/upper torso/forearms
• erythematous scaling papules polycyclic/arcuat
  e plaques
• no scarring/alopecia or follicular plugging
• photosensitive eruption
• 70 SSA/B
• 85 ANA

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SCLE Ddx

• psoriasis
• erythema multiforme
• polymorphous light eruption

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SLE Drug-induced

• 90 anti histone Ab
• 20 skin lesions

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SLE Drug-induced/aggravated/un-masked

• Sulfonylurea
• Griseofulvin
• Piroxicam
• Beta blockers
• Carbamazepine
• Estrogens
• Lithium
• Methyldopa
• Minoxidil
• Phenytoin
• PTU
• Quinidine
• Testosterone

• Ca channel blockers
• PUVA
• ACE inhibitors
• Hyrdralazine
• Procainamide
• Isoniazid
• Chlorpromazine
• Minocycline
• HCTZ
• Lamisil
• D-penicillamine
• Interferon
• -Statins

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Lupus Erythematosus Tx

• broad spectrum sun protection
• sunblock for lips
• sun avoidance
• physical protection
• monitor for systemic involvement

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Lupus Erythematosus Tx

• topical corticosteroids
• higher potencies for discoid LE
• antimalarials
• G6PD

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Dermatomyositis

• idiopathic inflammatory myopathy
• 1/100,000
• 21 female to male
• malignancy assoc. 15-25
• immune complex deposition in vessels

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Five diagnostic criteria

• Sym proxl muscle wknss
• Typical rash
• muscle enzymes
• EMG abn
• Muscle bx abn

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Gottron's sign

• symmetric,
• nonscaling
• violaceous erythematous eruption
• extensor surfaces MCP/IP/elbows/knee joints

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Dermatomyositis

• Diffuse flat erythema
• photosensitive

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Dermatomyositis

• Heliotrope rash
• is a reddishviolaceous eruption on the upper
  eyelids
• often accompanied by swelling of the eyelid

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Dermatomyositis

• Periungual erythema
• Painful roughening and cracking fingers termed
  "mechanic's hands

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Juvenile dermatomyositis a retrospective
review Pelero TM J Am Acad Dermatol 200l 45
of a 30-year experience
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Dermatomyositis Overlap

• Systemic lupus erythematosus
• Rheumatoid arthritis
• Sjögren's syndrome
• Dermatomyositis sine myositis or amyopathic
  dermatomyositis

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Dermatomyositis

• Muscle enzymes CK,LDH, AST,ALT,aldolase
• ANA 80
• anti-RNP - overlapmixed connective tissue
• anti-Jo Ab 30
• anti-Mi-2 Ab

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Dermatomyositis

• EMG - directing biopsy site biopsy
• Muscle biopsy - definitive test
• MR imaging and P-31 MR spectroscopy (MRS)

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Thickened, sclerotic skin lesions

• musculoskeletal,vasculature
• renal, pulmonary, cardiac, gi
• 4 to 253 / 1,000,000

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Scleroderma

• variable sclerosis
• hands and face

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CREST syndrome

• Calcinosis
• Raynaud's
• Esoph dysmotility
• Sclerodactyly
• Telangiectasia

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Sjogrens Syndrome

• xerosis with pruritus
• hyperpigmentation

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Sarcoidosis

• sarco-flesh
• eidos-like
• osis-condition

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Sarcoidosis

• multisystem disease of unknown etiology
• lymphocytes/mononuclear phagocytes form
  noncaseating granulomas
• 2yrs chronic

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Sarcoidosis

• highest incidence AA US females 30-39 y/o
• 107/100,000
• high in Sweden

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Sarcoidosis

• 25 present with skin findings
• Erythema nodosum-good prognosis

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Sarcoidosis

• asymptomatic
• waxy red/brown papules, macules, plaques, nodules
• sub q nodules, infiltrative scars

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Sarcoidosis

• face
• lips nape of neck
• upper back
• extremities

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Sarcoidosis-Lupus pernio

• AA
• fibrotic disease
• nose, lips, cheeks, ears
• respiratory tract involvement
• uveitis
• bone cysts

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Sarcoidosis

• acquired ichthyosis-DDX
• lumphoma
• solid malignancy
• HIV
• mycobacterial inf
• medically induced CTD
• thryoid/parathyroid
• malnutrition

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Sarcoidosis-Diff Dx

• syphilis

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Sarcoidosis

• Lofgrens Syndrome
• erythema nodosum
• bilat hilar adenopathy
• /- pulmonary fibrosis
• migratory polyarthritis
• fever
• uveitis

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Sarcoidosis-Tx

• Potent topical corticosteroids
• Intralesional corticosteroids
• Prednisone
• Antimalarials
• Methotrexate

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II. Hypersensitivity- Erythema Nodosum

• Defn Hypersensitivity reaction involving
  subcutaneous fat
• Morphology Erythematous nodules Location
  Extensor surfaces
• Epidemiology Females
• Natural history Individual lesions last 2 wks.

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Erythema Nodosum- Features

• Preceding uri
• Low grade fever
• Malaise
• Arthralgias 50

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Erythema Nodosum-Etiology

• Infections
• URI/Strep
• TB
• Coccidiodomycosis
• Yersiniosis
• others
• Lymphoma/leukemia
• 30-50 Idiopathic

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Erythema Nodosum-Etiology

• Drugs
• Sulfonamides
• Oral contraceptives
• Pregnancy
• Inflammatory Bowel Disease
• Sarcoidosis

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Erythema Nodosum-Patient Evaluation

• CXR-hilar lymphadenopathy may be seen in EN w/o
  sarcoidosis
• Throat culture/ASO titer
• PPD skin test
• ESR
• Stool culture if gi symptoms
• Excisional biopsy rarely indicated

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Erythema Nodosum-Differential Diagnosis

• Weber-Christian panniculitis suppurate/heal
  abnormally
• Thrombophlebitis
• Erysipelas
• Pancreatic induced panniculitis
• Erythema induratum-TB associated/ calves

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Erythema Nodosum-Treatment

• Naproxen/indomethacin/salicylates
• Bed rest
• Prednisone
• Potassium iodide

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Pyoderma Gangrenosum

• Defn Ulcerating skin disease
• Population Adults
• Distribution Lower legs, but anywhere
• Morphology
• Tender red papules and pustules dusky
  red/indurated nodules necrotic ulcer
• with undermined purple margin
• Cribiform scarring

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Pyoderma Gangrenosum- Etiology

• Inflammatory Bowel Disease
• Malignancy
• Rheumatoid arthritis
• IgA monoclonal gammopathy
• Lymphoreticular malignancy
• 40-50 unknown

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Pyoderma Gangrenosum-Diagnosis

• Clinical appearance
• Diagnosis of exclusion
• Skin biopsy for routine and cultures
• Fungal, AFB, mycobacteria, bacterial
• SPEP/IEP

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Pyoderma Gangrenosum-Treatment

• Avoid trauma
• Intralesional triamcinolone 10-25mg/cc
• Clobetasol proprionate 0.05 ointment under
  occlusion
• Prednisone
• Minocycline
• Dapsone
• Local care

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Pruritus of Unknown Origin

• Rashless

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Pruritus of unknown origin a retrospective
studyZirwas MJ, J Am Acad Dermatol 200145(6)
892-6

• University dermatology department
• 50 chart reviews
• 11 systemic cause
• 7 initial symptom of systemic disease

Hypothyroidism Gastric adenocarcinoma Hepatitis
C HIV Laryngeal carcinoma GVH CLL
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Initial Evaluation

• Any close contacts affected?
• Yesscabies
• NO?-Review of systems/medication review
• 2 weeks of mild skin care regimen

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Initial Evaluation

• Medication review
• opiates, aspirin, quinidine, phenothiazines,
  hormones, antimalarials
• ROS
• Social history- exposure to fiberglass,
  chemicals
• Full cutaneous exam

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Initial Evaluation

• Mild Skin Care Regimen
• Unscented white Dove soap
• Avoid prolonged, hot showers/baths
• Emollients applied immediately after shower or
  bath
• Cetaphil, Eucerin, Lubriderm, Moisturel

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Initial Evaluation

• Mild Skin Care Regimen (contd)
• Cotton clothing washed in mild laundry detergent
• Whisk Free, Ivory Snow Flakes, etc.
• avoid any fabric softeners, anti-wrinkle sheets
• Triamcinolone ointment or cream 0.1 one pound
  jar
• educate to apply over emollients bid/tid,
  avoiding face and groin

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F/U Evaluation

• Repeat ROS/Medication review
• Pruritus work up
• cbc
• u/a
• liver and kidney panel
• thyroid functions
• chest x ray
• age and/or symptom appropriate cancer screening

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Special Testing

• Secondary tests
• HIV
• SPEP/IEP
• stool for ova and parasites
• skin biopsy -routine and DIF

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Bibliography

• Patel P, Werth. Cutaneous lupus erythematosus a
  review. Dermatologic Clinics 2002 203 373-85
• McCauliffe, DP, Sontheimer, RD. Cutaneous Lupus
  Erythematosus. In The Clinical Management of
  Systemic Lupus Erythematosus, 2d ed, Schur, PH
  (Ed), Lippincott, Philadelphia 1996
• Requena L - Panniculitis. Part I. Mostly septal
  panniculitis.J Am Acad Dermatol 2001 45(2)
  163-83

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Bibliography

• Sontheimer RD Dermatomyositis an overview of
  recent progress with emphasis on dermatologic
  aspects. Dermatol Clin - 2002 20(3) 387-408
• Stonecipher, MR, Jorizzo, JL, White, WL, et al.
  Cutaneous changes of dermatomyositis in patients
  with normal muscle enzymes dermatomyositis sine
  myositis? J Am Acad Dermatol 1993 28951.
• English JC, Patel PJ, Greer KE. Sarcoidosis. J Am
  Acad Dermatol 2001 44 725-43.
• Etter L, Myers SA. Pruritus in systemic disease
  mechanisms and management. Dermatologic Clinics
  200220(3) 459-72
• Srivastava M - Drug-induced, Ro/SSA-positive
  cutaneous lupus erythematosus. Arch Dermatol -
  2003 139(1) 45-9