Cutaneous Manifestations of Internal Disease

Adam O. Goldstein, MD, MPH

Associate Professor

Family Medicine

University of North Carolina

at Chapel Hill

aog@med.unc.edu

Cutaneous Manifestations of Internal Disease

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

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)

Large/medium Vessel Vasculitis

Clinical Presentation» livedo reticularis» subcutaneous nodules

(malleoli/post calf)» papulonecrotic lesions» digital infarctions» ulcers» ecchymosis

Differential Diagnosis

Polyarteritis nodosa

Wegener’s Granulomatosis

Churg-Strauss Syndrome

Small Vessel Vasculitis

Morphology» palpable purpura» urticaria» hemorrhagic pustules» nodules, bullae or ulcers

Features» fever, malaise, myalgia, » arthralgia, lower ext. edema

Differential Diagnosis/ Etiologies

» Infections: Hepatitis B/C, acute Strep, viral URI

» ANCA

» Henoch-Schonlein Purpura

» Connective Tissue Disease

» Neoplasms

Differential Dx & Etiologies

» Cryoglobulinemia

» Hypersensitivity

» Medications:– penicillin, thiazides,

aspirin, phenothiazines, sulfonamides, iodides

» Unknown

Schamberg’s 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

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

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.

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.

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

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.

Patient Evaluation

» Identify and confirm source of offending antigen (drug/infection)

» throat culture/ASO titer» ESR/CBC w/plt» Creatinine» U/A» ANA

Patient Evaluation (cont’d)

SPEP/IEP Hepatitis B/C screening CH50

Cryoglobulins Rheumatoid Factor

Patient Evaluation (cont’d)

Skin biopsy from new lesions (<24-48 hrs. old)» lumph predominate -CTD/

eos-Churg-Strauss» Immunofluorescent studies if

concerned about HSP(IgA)– special media required

CXR

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

Rheumatologic Diseases

Lupus erythematosus Dermatomyositis Scleroderma Sjogren’s Syndrome

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.

Lupus Erythematosus

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

Diagnosis of SLE

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

Specific findings

discoid malar rash photosensitivity oral ulcers

Nonspecific findings

vasculitis urticarial vasculitis alopecia calcinosis cutis rhematoid nodules Raynaud’s

Discoid LE

distribution: sun-exposed face and scalp papules, plaques erythema, pigmentary

alteration, scarring, follicular plugging

Discoid LE: Ddx

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

Discoid LE: Dx

biopsy ANA CBC w/diff esr, BUN/Cr/u/a <5% have SLE

SLE

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

Lupus Profundus

•3% w/ chronic cutaneous lupus

•More frequent in women

•Upper arms, shoulders, face, and buttocks

•Often trauma related

•Dx-biopsy

SLE Ddx

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

SLE Ddx

seborrhea» paranasal scaling» look for scalp/eyebrow involvement

SLE Ddx

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

SLE Dx

ANAcbc/esr/cr/bun/u/a+/- biopsy if other unclear

SLE Lab Dx

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

Photosensitivity

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

Oral Ulcers

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

SCLE

10% of all SLE

older milder

disease

SCLE

face/neck/upper torso/forearms erythematous scaling papules

>>>>polycyclic/arcuate plaques no scarring/alopecia or follicular

plugging photosensitive eruption 70% SSA/B + 85% ANA +

SCLE Ddx

psoriasis erythema multiforme polymorphous light eruption

SLE: Drug-induced

90% anti histone Ab

20% skin lesions

<8% SLE caused by drugs

SLE: Drug-induced/aggravated/un-masked

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

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

Lupus Erythematosus Tx

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

Lupus Erythematosus Tx

topical corticosteroids

»higher potencies for discoid LE antimalarials

»G6PD

Dermatomyositis

idiopathic inflammatory myopathy 1/100,000 2:1 female to male malignancy assoc. 15-25% immune complex deposition in vessels

Five diagnostic criteria

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

Gottron's sign

symmetric, nonscaling violaceous

erythematous eruption

extensor surfaces MCP/IP/elbows/knee joints

Dermatomyositis

Diffuse flat erythema photosensitive

Dermatomyositis

Heliotrope rash» is a reddish–violaceous eruption on the

upper eyelids» often accompanied by swelling of the

eyelid

Dermatomyositis

Periungual erythema Painful roughening and

cracking fingers termed "mechanic's hands”

of a 30-year experience

Juvenile dermatomyositis: a retrospective reviewPelero TM J Am Acad Dermatol 200l; 45

Dermatomyositis Overlap

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

amyopathic dermatomyositis

Dermatomyositis

Muscle enzymes — CK,LDH, AST,ALT,aldolase

ANA 80% anti-RNP - overlap=mixed connective

tissue anti-Jo Ab 30% anti-Mi-2 Ab

Dermatomyositis

EMG - directing biopsy site biopsy

Muscle biopsy - definitive test

MR imaging and P-31 MR spectroscopy (MRS)

Thickened, sclerotic skin lesions

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

Scleroderma

variable sclerosis hands and face

CREST syndrome

Calcinosis Raynaud's Esoph dysmotility Sclerodactyly Telangiectasia

Sjogren’s Syndrome

xerosis with pruritus hyperpigmentation

Sarcoidosis

sarco-flesh eidos-like osis-condition

Sarcoidosis

multisystem disease of unknown etiology lymphocytes/mononuclear phagocytes form

noncaseating granulomas >2yrs = chronic

Sarcoidosis

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

Sarcoidosis

25% present with skin findings Erythema nodosum-good prognosis

Sarcoidosis

asymptomatic waxy red/brown papules, macules,

plaques, nodules sub q nodules, infiltrative scars

Sarcoidosis

face lips nape of neck upper back extremities

Sarcoidosis-Lupus pernio

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

Sarcoidosis

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

Sarcoidosis-Diff Dx

syphilis

Sarcoidosis

Lofgren’s Syndrome» erythema nodosum» bilat hilar adenopathy» +/- pulmonary fibrosis» migratory polyarthritis» fever» uveitis

Sarcoidosis-Tx

Potent topical corticosteroids Intralesional corticosteroids Prednisone Antimalarials Methotrexate

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.

Erythema Nodosum- Features

Preceding uri Low grade fever Malaise Arthralgias 50%

Erythema Nodosum-Etiology

Infections» URI/Strep» TB» Coccidiodomycosis» Yersiniosis» others

Lymphoma/leukemia 30-50% Idiopathic

Erythema Nodosum-Etiology

Drugs» Sulfonamides» Oral contraceptives

Pregnancy Inflammatory Bowel Disease Sarcoidosis

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

Erythema Nodosum-Differential Diagnosis

Weber-Christian panniculitis: suppurate/heal abnormally

Thrombophlebitis Erysipelas Pancreatic induced panniculitis Erythema induratum-TB associated/

calves

Erythema Nodosum-Treatment

Naproxen/indomethacin/salicylates Bed rest Prednisone Potassium iodide

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

Pyoderma Gangrenosum- Etiology

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

Pyoderma Gangrenosum-Diagnosis

Clinical appearance Diagnosis of exclusion Skin biopsy for routine

and cultures

» Fungal, AFB, mycobacteria, bacterial

SPEP/IEP

Pyoderma Gangrenosum-Treatment

Avoid trauma Intralesional triamcinolone: 10-25mg/cc Clobetasol proprionate 0.05% ointment

under occlusion Prednisone Minocycline Dapsone Local care

Pruritus of Unknown Origin

Rashless

Pruritus of unknown origin: a retrospective study

Zirwas MJ, J Am Acad Dermatol 2001;45(6) 892-6

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

HypothyroidismGastric adenocarcinomaHepatitis CHIVLaryngeal carcinomaGVHCLL

Initial Evaluation

Any close contacts affected? » Yes>>>>scabies» NO?-Review of systems/medication review

2 weeks of mild skin care regimen

Initial Evaluation

Medication review» opiates, aspirin, quinidine, phenothiazines,

hormones, antimalarials ROS Social history- exposure to fiberglass,

chemicals Full cutaneous exam

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

Initial Evaluation

Mild Skin Care Regimen (cont’d)

» 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

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

Special Testing

Secondary tests

» HIV

» SPEP/IEP

» stool for ova and parasites

» skin biopsy -routine and DIF

Bibliography

Patel P, Werth. Cutaneous lupus erythematosus: a review. Dermatologic Clinics 2002; 20;3: 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

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; 28:951.

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 2002;20(3): 459-72

Srivastava M - Drug-induced, Ro/SSA-positive cutaneous lupus erythematosus. Arch Dermatol - 2003; 139(1): 45-9