Transcript Cutaneous Manifestations of Systemic Diseases

Cutaneous
Manifestations of
Systemic Diseases
Hayden 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
Systemic Lupus Erythematosus
 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
Systemic Lupus Erythematosus
 Malar (Butterfly) rash is the “classic presentation”
 May be distinct or subtle
Systemic Lupus Erythematosus
 Fixed erythema, flat or raised, over malar eminences
 Spares the Nasolabial Folds
Systemic Lupus Erythematosus
 Discoid Rash is “classic” as well
Systemic Lupus Erythematosus
 Erythematous, patches and plaques, with adherent scales,
follicular plugging and atrophic scarring
Systemic Lupus Erythematosus
 Photosensitivity – rash as an unusual reaction to sunlight
Systemic Lupus Erythematosus
 Oral Ulcers – usually painless and may be nasopharyngeal
Systemic Lupus Erythematosus
 Presentation isn’t always “classic”
 High index of suspicion
 Alopecia and rash may be anywhere on skin
Systemic Lupus Erythematosus
 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)
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
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
Rheumatoid Arthritis
 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 Arthritis
 Rheumatoid Nodules – discrete, non tender subcutaneous
tumors
Rheumatoid Arthritis
 Vascular Lesions – erythema of palms and digital infarcts
Rheumatoid Arthritis
Rheumatoid Arthritis
 Gravitational ulcers – most common
 Arteritic ulcers – actually rare until advanced disease
Rheumatoid Arthritis
 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
 Necrobiosis Lipoidica Diabeticorum
 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
 Necrobiosis Lipoidica Diabeticorum
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
Thyroid Disease (Hypothyroidism)
Thyroid Disease (Hypothyroidism)
 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
Thyroid Disease (Hypothyroidism)
CARDIOPULMONARY DISEASES
 Coronary Heart Disease
 Subacute Bacterial Endocarditis
 COPD
 Cystic Fibrosis
 Asthma
Coronary Heart Disease
 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
Coronary Heart Disease
 Xanthomatosis
Coronary Heart Disease
 Earlobe Crease
Coronary Heart Disease
 Postbypass Skin Changes –
 Saphenous Vein Graft Site Dermatitis
 Tinea Pedis
 Stasis Edema and Stasis Dermatitis
Coronary Heart Disease
 Saphenous Vein Graft Site Dermatitis
Coronary Heart Disease
 Tinea Pedis
Coronary Heart Disease
 Stasis Edema and Stasis Dermatitis
Coronary Heart Disease
 Stasis Edema and Stasis Dermatitis
Coronary Heart Disease
 Stasis Dermatitis vs Cellulitis
Actinic Purpura
Subacute Bacterial Endocarditis
 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)
Subacute Bacterial Endocarditis
 Petechiae
Subacute Bacterial Endocarditis
 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
Subacute Bacterial Endocarditis
 Subungual Splinter Hemorrhages
Subacute Bacterial Endocarditis
 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)
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)
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
Pyoderma Gangrenosum
 Pyoderma Gangrenosum
Pyoderma Gangrenosum
 Pyoderma Gangrenosum
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
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
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
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
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)
Parkinson’s Disease
 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
Parkinson’s Disease
 Hyperhidrosis especially of the face and palms
 Peripheral sweat gland function is controlled by sympathetic
nervous system which is altered in PD patients
Parkinson’s Disease
 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
Parkinson’s Disease
 Seborrheic Dermatitis
Cerebrovascular Accident (Stroke)
 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)
Cerebrovascular Accident (Stroke)
Cerebrovascular Accident (Stroke)
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
 Lupus Pernio
Sarcoidosis
 Erythema Nodosum