Cutaneous Manifestations of Systemic Diseases Hayden H. Franks, MD June 13, 2013.

Cutaneous Manifestations of

Systemic DiseasesHayden H. Franks, MD

June 13, 2013

Who Is This Guy?

Private practice Dermatologist

Clinics in Little Rock and Texarkana

Fellow of the American Academy of Dermatology

Diplomate of the American Board of Dermatology

Assistant Clinical Professor of Dermatology, UAMS AHEC SW

Honorary Member of the Arkansas Academy of Family Physicians

Disease Categories

Autoimmune Diseases

Endocrine Diseases

Cardiopulmonary Diseases

Gastrointestinal Diseases

Neurological Diseases

Diseases not Otherwise Specifiied

Cutaneous Manifestations of Systemic Diseases

Frequently encountered

May be the initial sign of internal disease

May occur late in the course of the disease

May assist in making the diagnosis

May be obvious or subtle

Overlap of Family Practice and Dermatology

AUTOIMMUNE DISEASES

Systemic Lupus Erythematosus

Scleroderma

Dermatomyositis

Rheumatoid Arthritis


Autoimmune, systemic disease affecting multiple organ systems

The most common connective tissue disease

Especially prevalent in black women – Prevalence 1/250

Cutaneous lesions present in 85% of patients

Of the 11 Classic Criteria for diagnosing SLE, 4 involve the skin or mucus membranes


Malar (Butterfly) rash is the “classic presentation”

May be distinct or subtle


Fixed erythema, flat or raised, over malar eminences

Spares the Nasolabial Folds


Discoid Rash is “classic” as well


Erythematous, patches and plaques, with adherent scales, follicular plugging and atrophic scarring


Photosensitivity – rash as an unusual reaction to sunlight


Oral Ulcers – usually painless and may be nasopharyngeal


Presentation isn’t always “classic”

High index of suspicion

Alopecia and rash may be anywhere on skin


Diagnosis is based on presence of multisystem disease and presence of antinuclear antibodies

Treatment is multifactorial with corticosteroids being the mainstay still

Sunscreen

Antimalarials, methotrexate, dapsone and biologics now are commonly used

Scleroderma

Chronic autoimmune disease of unknown cause that affects the microvasculature and loose connective tissue

Characterized by fibrosis and obliteration of vessels in skin, lungs, GI tract, kidneys and heart

May be localized (Morphea) or systemic (Systemic Scleroderma)

Scleroderma (Morphea)

Morphea – benign and self limited

Usually single or few in number

Red, then white, atrophic, indurated with alopecia

Scleroderma (Morphea)

Treatment is unsatisfactory

Topical or intralesional steroids, PUVA

Systemic Scleroderma (SSc)

Four times more common in women

10 year survival rate of 21-71%

Clinical manifestations depend on the sites involved

Initial complaints are usually Raynaud’s phenomenon or chronic, non pitting edema of hands and fingers or migratory polyarthritis

Disease may extend to involve upper extremities, trunk, face and finally the lower extremities

Systemic Scleroderma (SSc)

Systemic Scleroderma (SSc) Diagnosis

Autoantibodies to Fibrillin 1, Rheumatoid Factor, Anti SS DNA, Anti RNA Polymerase 3, Antitopoisomerase 1, Anticentromere Antibodies

Skin Biopsy

Systemic Scleroderma (SSc) Treatment

Treatment is unsatisfactory

Immunosuppressive Drugs of numerous types

Methotrexate, Cyclosporine, Imuran

Biologics

Dermatomyositis

The most common idiopathic inflammatory myopathy

May occur at any age

Unknown etiology

Autoimmune Disease

Progressive weakness of trunk and major limb muscles

Difficulty in rising from a chair or climbing stairs

Impaired mobility and some muscle tenderness

Dermatomyositis

Bilateral muscle weakness that is progressive

Skin lesions are almost always present from the onset

Maculopapular erythema over bony prominences such as the knuckles, elbows and knees

Red to violaceous plaques with telangiectasias and scales

Gottron’s Papules – polymorphic, erythematous and atrophic plaques

Dermatomyositis

Dermatomyositis

Heliotrope Rash – Periorbital erythema

Nail Margin Telangiectasias

Dermatomyositis Diagnosis

Elevated serum muscle enzymes (CK) and Aldolase

Antinuclear Antibodies

Muscle biopsy – segmental muscle fiber fibrosis, interstitial inflammation and vasculopathy

Skin biopsy – Focal vacuolar degeneration of basal cells, basement membrane degeneration and epidermal atrophy

Dermatomyositis Treatment

Primary treatment remains Prednisone 1mg/kg/day

Plasmapheresis

Cyclosporine

Dapsone

?Biologics

Physical Therapy


Disease affects up to 2% of adult women

Onset is sudden or insidious

Symmetric polyarthritis that affects the proximal interphalangeal and metacarpophalangeal joints, the wrists, ankles, knees and cervical spine

Stiffness, painful, warm and tender joints

Fever, weight loss and anemia are prominent


Rheumatoid Nodules – discrete, non tender subcutaneous tumors


Vascular Lesions – erythema of palms and digital infarcts


Gravitational ulcers – most common

Arteritic ulcers – actually rare until advanced disease


Laboratory Workup – Rheumatoid Factor and ANA

Treatment – Prednisone, Methotrexate, Biologics

ENDOCRINE DISEASES

Diabetes Mellitus

Thyroid Disease

Diabetes Mellitus

The skin shares both in the effects of acute metabolic derangements and in the chronic degenerative complications of diabetes.

Diabetes Mellitus

Infection

Diabetic Dermopathy

Thickened skin, stiff joints and Scleredema Adultorum

Necrobiosis Lipoidica Diabeticorum

Vitiligo

Acanthosis Nigricans

Kyrle’s Disease (Reactive Perforating Collagenosis)

Diabetes Mellitus

Bacterial and fungal infections

Furunculosis, Cellulitis, Erythrasma, and Candidiasis

Hyperglycemia leads to abnormalities in leukocyte function including diminished chemotaxis and phagocytosis

Diabetes Mellitus

Bacterial Infections

Diabetes Mellitus

Cellulitis

Diabetes Mellitus

Erythrasma

Diabetes Mellitus

Candidiasis

Diabetes Mellitus

Diabetic Dermopathy – atrophic, circumscribed brownish lesions usually on the lower extremities

They resemble post traumatic scarring

Diabetes Mellitus

Thickened Skin, Stiff Joints and Scleredema Adultorum

33% of Diabetics have tight, indurated and waxy skin over the dorsa of the hands

Scleredema Adultorum is strongly correlated with IDDM

Consists of induration of the skin beginning on the posterior and lateral aspect of the neck, is painless and may be progressive

Diabetes Mellitus

Diabetes Mellitus

Scleredema Adultorum

Diabetes Mellitus


Occurs in 0.3% of IDDM Patients

Very distinct

Asymptomatic, atrophic, yellow to brown patches classically on the lower extremities

Telangiectasias are prominent

Diabetes Mellitus


Diabetes Mellitus

Vitiligo

Many times is associated with IDDM, Thyroid Disease and Systemic Lupus Erythematosus

Diabetes Mellitus

Acanthosis Nigricans – characterized as velvety, papillomatous hyperplasia of the epidermis with intense hyperpigmentation

Axillary, inguinal and inframammary folds and the neck

Found in association with several endocrinopathies – including Cushing’s Disease, Polycystic Ovary Disease and IDDM

Diabetes Mellitus

Acanthosis Nigricans

Diabetes Mellitus

Kyrle’s Disease – rare and characterized by hyperkeratotic, follicular and perifollicular papules

Transepidermal elimination of altered collagen

Also strongly associated with renal disease

Diabetes Mellitus

Kyrle’s Disease

Thyroid Disease

Thyroid hormones have diverse primary sites of action at the level of the cell membrane, mitochondria and gene transcription that regulate functional properties and metabolism of most cells of the body including the keratinocytes and fibroblasts of the skin.

Thyroid hormones affect production of collagen and mucopolysacccharides by dermal fibroblasts.

Lack of thyroid hormone affects all of the above

Excess thyroid hormone does not

Thyroid Disease

Thyrotoxicosis (Hyperthyroidism) – due to Grave’s Disease or Toxic Nodular Goiter

Skin is warm, moist, flushed and excess sweating

Alopecia

Uncommonly pruritus, vitiligo

Pretibial Myxedema

Thyroid Disease

Pretibial Myxedema – an infiltrative dermopathy, usually over anterior tibia and dorsa of feet.

Bilateral, pink, violacous or flesh colored confluent papules

Diffuse brawny edema

Correction of thyrotoxicosis has no effect on the skin lesions

Half of cases occur after patient has been rendered euthyroid

Thyroid Disease

Pretibial Myxedema

Thyroid Disease (Hypothyroidism)

Skin is cold, xerotic and pale

Vasoconstriction

Epidermis is thin, hyperkeratotic

Fine wrinkling resembles parchment paper

Yellow discoloration especially of palms, soles and nasolabial folds

Hair is dry, coarse, brittle and grows slowly


Myxedema – dermal accumulation of mucopolysaccharides (hyaluronic acid and chondroitin sulfate)

Usually located acrally

May be diffuse or focal (papules)

Broad nose, thick lips, large smooth tongue

Drooping eyelids and an expressionless face

CARDIOPULMONARY DISEASES

Coronary Heart Disease

Subacute Bacterial Endocarditis

COPD

Cystic Fibrosis

Asthma


Familial Hyperlipidemia – a group of metabolic disorders with elevated plasma cholesterol and or triglyceride levels. Often see Xanthomatosis on the skin

Earlobe Crease – there is an association between CAD and a diagonally positioned skin crease along the earlobe that may be unilateral or bilateral.

Post Bypass Skin changes


Xanthomatosis


Earlobe Crease


Postbypass Skin Changes –

Saphenous Vein Graft Site Dermatitis

Tinea Pedis

Stasis Edema and Stasis Dermatitis


Saphenous Vein Graft Site Dermatitis


Tinea Pedis


Stasis Edema and Stasis Dermatitis


Stasis Dermatitis vs Cellulitis

Actinic Purpura


Petechiae are the most common mucocutaneous manifestation of bacterial endocarditis – small red or violaceous macules that don’t blanch – not associated with platelet dysfunction Osler’s Nodes Janeway Lesions Subungual Splinter Hemorrhages Cutaneous Purpura and Petechiae Conjunctival Petechiae (Roth’s Spots)


Petechiae


Osler’s Nodes – painful hemorrhagic macules and papules located on digital tufts

Subacute Bacterial Endocaridits

Janeway Lesions- Nontender hemorrhagic macules and papules located on palms and soles


Subungual Splinter Hemorrhages


Conjunctival Petechiae (Roth’s Spots)

Chronic Obstructive Pulmonary Disease (COPD)

Actually a group of disorders including chronic bronchitis, bronchiectasis, emphysema and asthma

Incidence is increasing and actually approaching that of cardiac disease

Environmental and genetic influences

Chronic Obstructive Pulmonary Disease (COPD)

Cystic Fibrosis

Autosomal Recessive disorder of the exocrine glands that subsequently involves the tracheobronchial tree, pancreas and GI tract

Cutaneous features result from increased amounts of electrolyte in the sweat that leads to excess skin wrinkling of palms and soles when immersed in water.

Cystic Fibrosis

Asthma

Asthma – Eczema Complex (Atopy) Association of asthma, atopic eczema and

allergic rhinitis are well documented Mediators of this inflammatory response may

be released by sensitized IgE – Mast cell complexes

Dust, pollen, dander, heat, dry conditions, exercise and other allergens all may trigger an outbreak

Asthma

Asthma – Atopic Dermatitis (Atopy)

GASTROINTESTINAL DISEASES

Inflammatory Bowel Disease

Celiac Disease

Hepatitis

Cutaneous Manifestations of Gastrointestinal Diseases

Jaundice

Melanosis

Nail Changes

Edema

Purpura

Pruritus

Vascular Changes Spider

Telangiectasias Palmar Erythema

Inflammatory Bowel Disease

Inflammatory Bowel Disease – Ulcerative Colitis and Crohn’s Disease

Skin complications are similar in these two diseases

Pyoderma Gangrenosum Erythema Nodosum Aphthous Ulcers Lichen Planus

Pyoderma Gangrenosum

Pyoderma Gangrenosum Rare, destructive, inflammatory skin disease Progressively enlarging ulcers with raised,

tender, undermined borders Most commonly seen on legs but may be

anywhere May be solitary or multiple May be isolated or seen with Inflammatory

Bowel Disease, Polyarthritis or certain malignancies

Affects 5 to 10% of Inflammatory Bowel Disease patients

Erythema Nodosum

Erythema Nodosum Cutaneous reaction pattern consisting of

inflammatory, spontaneously regressing, tender, nodular lesions located primarily over the extensor surfaces of the lower legs

Septal panniculitis without vasculitis Is associated with a wide variety of disease

processes Immunologic pathogenesis In addition to occurring in Crohn’s and UC,

also seen with infections, Sarcoidosis and drugs (Sulfonamides and Oral Contraceptives )

Erythema Nodosum

Erythema Nodosum

Aphthous Ulcers

Aphthous Ulcers Small, shallow, well circumscribed ulcers Oral mucosa Appear suddenly and are painful Resolve within 2 weeks only to recur May be related to stress or menses Very common – may affect up to 20% of

general population

Aphthous Ulcers

Aphthous Ulcers

Lichen Planus

Lichen Planus Skin eruption consisting of violaceous,

scaling, angular papules and plaques Flexor surfaces and mucus membranes are

classic locations Symmetrically distributed Usually pruritic Incidence of around 0.5% Usually isolated but may be associated with

underlying disease (UC and Crohn’s Disease)

Lichen Planus

Lichen Planus

Celiac Disease

Celiac Disease – also known as Celiac Sprue. autoimmune disease of the small intestine Abdominal pain, discomfort, diarrhea,

constipation, failure to thrive (children) May lead to vitamin deficiencies due to

malabsorption Increasing in incidence due to improved

screening Associated with Dermatitis Herpetiformis

Dermatitis Herpetiformis

Dermatitis Herpetiformis Intensely pruritic, chronic, papulovesicular

eruption distributed symmetrically on extensor surfaces classically over the elbow

Most patients have an associated gluten sensitive enteropathy that may be asymptomatic

Universally responsive to Dapsone Most patients with DH have Celiac Disease

although many are mild or asymptomatic Gluten free diet is beneficial

Dermatitis Herpetiformis

Cutaneous Manifestations of Hepatitis

Urticaria

Vasculitis

Polyarteritis Nodosa

Relapsing Papulovesicular Rash

Urticaria in Hepatitis

Vasculitis in Hepatitis

NEUROLOGICAL DISEASES

Parkinson’s Disease

Cerebrovascular Accident (Stroke)


Degenerative disorder of the Central Nervous System

Motor symptoms result from death of Substantia Nigra cells of the Midbrain which generate Dopamine

Tremor at rest, bradykinesia, rigidity, postural instability

Later in disease dementia and neuropsychiatric problems may occur


Hyperhidrosis especially of the face and palms Peripheral sweat gland function is controlled

by sympathetic nervous system which is altered in PD patients


Seborrheic Dermatitis Overexcretion of sebum on the face which is

thought to be caused by hyperactivity of the Parasympathetic component of the Autonomic Nervous System


Seborrheic Dermatitis


Changes are due to Unilateral disturbance in autonomic function -

including skin temperature, turgor, xerosis and sweating

Loss of motor function –including edema and ulceration (pressure ulcers)

DISEASES NOT OTHERWISE SPECIFIED

Sarcoidosis

Sarcoidosis

A granulomatous disease most commonly associated with lesions of the lungs and bilateral hilar lymphadenopathy

Multisystem disease that can present in many ways

1/3 of pateints complain of fatigue, fever and weight loss

1/3 of patients have dyspnea, cough and chest pain

Serum ACE levels raised in 60% of patients

Skin lesions occur in 40 % of patients

Sarcoidosis

Skin Lesions Lupus Pernio Skin Plaques Subcutaneous nodules Erythema Nodosum

Sarcoidosis

Lupus Pernio – the most characteristic of all Sarcoid skin lesions Chronic, violaceous, indurated papules and

plaques with a predilection for the face especially the nose

May be associated with advance pulmonary disease

Sarcoidosis

Lupus Pernio

Sarcoidosis

Erythema Nodosum

Cutaneous Manifestations of Systemic Diseases Hayden H. Franks, MD June 13, 2013.

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Transcript of Cutaneous Manifestations of Systemic Diseases Hayden H. Franks, MD June 13, 2013.