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

2. 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

3. Disease Categories Autoimmune Diseases Endocrine Diseases
Cardiopulmonary Diseases
Gastrointestinal Diseases
Neurological Diseases
Diseases not Otherwise Specifiied

4. 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

5. AUTOIMMUNE DISEASES Systemic Lupus Erythematosus Scleroderma
Dermatomyositis
Rheumatoid Arthritis

6. 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

7. Systemic Lupus Erythematosus
Malar (Butterfly) rash is the “classic presentation”
May be distinct or subtle

8. Systemic Lupus Erythematosus
Fixed erythema, flat or raised, over malar eminences
Spares the Nasolabial Folds

9. Systemic Lupus Erythematosus
Discoid Rash is “classic” as well

10. Systemic Lupus Erythematosus
Erythematous, patches and plaques, with adherent scales, follicular plugging and atrophic scarring

11. Systemic Lupus Erythematosus
Photosensitivity – rash as an unusual reaction to sunlight

12. Systemic Lupus Erythematosus
Oral Ulcers – usually painless and may be nasopharyngeal

13. Systemic Lupus Erythematosus
Presentation isn’t always “classic”
High index of suspicion
Alopecia and rash may be anywhere on skin

14. 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

15. 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)

16. Scleroderma (Morphea)
Morphea – benign and self limited
Usually single or few in number
Red, then white, atrophic, indurated with alopecia

17. Scleroderma (Morphea)
Treatment is unsatisfactory
Topical or intralesional steroids, PUVA

18. 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

19. Systemic Scleroderma (SSc)

20. Systemic Scleroderma (SSc)

21. Systemic Scleroderma (SSc)

22. Systemic Scleroderma (SSc) Diagnosis
Autoantibodies to Fibrillin 1, Rheumatoid Factor, Anti SS DNA, Anti RNA Polymerase 3, Antitopoisomerase 1, Anticentromere Antibodies
Skin Biopsy

23. Systemic Scleroderma (SSc) Treatment
Treatment is unsatisfactory
Immunosuppressive Drugs of numerous types
Methotrexate, Cyclosporine, Imuran
Biologics

24. 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

25. 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

26. Dermatomyositis

27. Dermatomyositis

28. Dermatomyositis Heliotrope Rash – Periorbital erythema
Nail Margin Telangiectasias

29. 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

30. Dermatomyositis Treatment
Primary treatment remains Prednisone 1mg/kg/day
Plasmapheresis
Cyclosporine
Dapsone
?Biologics
Physical Therapy

31. 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

32. Rheumatoid Arthritis
Rheumatoid Nodules – discrete, non tender subcutaneous tumors

33. Rheumatoid Arthritis
Vascular Lesions – erythema of palms and digital infarcts

34. Rheumatoid Arthritis

35. Rheumatoid Arthritis Gravitational ulcers – most common
Arteritic ulcers – actually rare until advanced disease

36. Rheumatoid Arthritis Laboratory Workup – Rheumatoid Factor and ANA
Treatment – Prednisone, Methotrexate, Biologics

37. ENDOCRINE DISEASES
Diabetes Mellitus
Thyroid Disease

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

39. Diabetes Mellitus Infection Diabetic Dermopathy
Thickened skin, stiff joints and Scleredema Adultorum
Necrobiosis Lipoidica Diabeticorum
Vitiligo
Acanthosis Nigricans
Kyrle’s Disease (Reactive Perforating Collagenosis)

40. Diabetes Mellitus Bacterial and fungal infections
Furunculosis, Cellulitis, Erythrasma, and Candidiasis
Hyperglycemia leads to abnormalities in leukocyte function including diminished chemotaxis and phagocytosis

41. Diabetes Mellitus
Bacterial Infections

42. Diabetes Mellitus
Cellulitis

43. Diabetes Mellitus
Erythrasma

44. Diabetes Mellitus
Candidiasis

45. Diabetes Mellitus
Diabetic Dermopathy – atrophic, circumscribed brownish lesions usually on the lower extremities
They resemble post traumatic scarring

46. 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

47. Diabetes Mellitus

48. Diabetes Mellitus
Scleredema Adultorum

49. 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

50. Diabetes Mellitus
Necrobiosis Lipoidica Diabeticorum

51. Diabetes Mellitus Vitiligo
Many times is associated with IDDM, Thyroid Disease and Systemic Lupus Erythematosus

52. 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

53. Diabetes Mellitus
Acanthosis Nigricans

54. 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

55. Diabetes Mellitus
Kyrle’s Disease

56. 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

57. 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

58. 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

59. Thyroid Disease
Pretibial Myxedema

60. 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

61. Thyroid Disease (Hypothyroidism)

62. 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

63. Thyroid Disease (Hypothyroidism)

64. CARDIOPULMONARY DISEASES
Coronary Heart Disease
Subacute Bacterial Endocarditis
COPD
Cystic Fibrosis
Asthma

65. 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

66. Coronary Heart Disease
Xanthomatosis

67. Coronary Heart Disease
Earlobe Crease

68. Coronary Heart Disease
Postbypass Skin Changes –
Saphenous Vein Graft Site Dermatitis
Tinea Pedis
Stasis Edema and Stasis Dermatitis

69. Coronary Heart Disease
Saphenous Vein Graft Site Dermatitis

70. Coronary Heart Disease
Tinea Pedis

71. Coronary Heart Disease
Stasis Edema and Stasis Dermatitis

72. Coronary Heart Disease
Stasis Edema and Stasis Dermatitis

73. Coronary Heart Disease
Stasis Dermatitis vs Cellulitis

74. Actinic Purpura

75. 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)

76. Subacute Bacterial Endocarditis
Petechiae

77. Subacute Bacterial Endocarditis
Osler’s Nodes – painful hemorrhagic macules and papules located on digital tufts

78. Subacute Bacterial Endocaridits
Janeway Lesions- Nontender hemorrhagic macules and papules located on palms and soles

79. Subacute Bacterial Endocarditis
Subungual Splinter Hemorrhages

80. Subacute Bacterial Endocarditis
Conjunctival Petechiae (Roth’s Spots)

81. 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

82. Chronic Obstructive Pulmonary Disease (COPD)

83. Chronic Obstructive Pulmonary Disease (COPD)

84. 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.

85. Cystic Fibrosis

86. 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

87. Asthma
Asthma – Atopic Dermatitis (Atopy)

88. Asthma
Asthma – Atopic Dermatitis (Atopy)

89. GASTROINTESTINAL DISEASES
Inflammatory Bowel Disease
Celiac Disease
Hepatitis

90. Cutaneous Manifestations of Gastrointestinal Diseases
Jaundice
Vascular Changes
Melanosis
Spider Telangiectasias
Palmar Erythema
Nail Changes
Edema
Purpura
Pruritus

91. 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

92. 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

93. Pyoderma Gangrenosum
Pyoderma Gangrenosum

94. Pyoderma Gangrenosum
Pyoderma Gangrenosum

95. 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 )

96. Erythema Nodosum
Erythema Nodosum

97. Erythema Nodosum
Erythema Nodosum

98. 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

99. Aphthous Ulcers
Aphthous Ulcers

100. Aphthous Ulcers
Aphthous Ulcers

101. 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)

102. Lichen Planus
Lichen Planus

103. Lichen Planus
Lichen Planus

104. 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

105. 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

106. Dermatitis Herpetiformis

107. Dermatitis Herpetiformis

108. Cutaneous Manifestations of Hepatitis
Urticaria
Vasculitis
Polyarteritis Nodosa
Relapsing Papulovesicular Rash

109. Urticaria in Hepatitis

110. Vasculitis in Hepatitis

111. NEUROLOGICAL DISEASES
Parkinson’s Disease
Cerebrovascular Accident (Stroke)

112. 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

113. 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

114. 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

115. Parkinson’s Disease
Seborrheic Dermatitis

116. 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)

117. Cerebrovascular Accident (Stroke)

118. Cerebrovascular Accident (Stroke)

119. DISEASES NOT OTHERWISE SPECIFIED
Sarcoidosis

120. 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

121. Sarcoidosis Skin Lesions Lupus Pernio Skin Plaques
Subcutaneous nodules
Erythema Nodosum

122. 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

123. Sarcoidosis
Lupus Pernio

124. Sarcoidosis
Lupus Pernio

125. Sarcoidosis
Erythema Nodosum