Cutaneous Manifestations of Systemic Diseases/Internal Cutaneous Manifestations of Systemic Diseases/Internal Malignancy/Vasculitis Jerry Tan MD FRCP University of W estern Ontario W

Objectives List cutaneous manifestations of common systemic diseases Recognize cutaneous signs suggestive of systemic disease and internal malignancies

Dermatologic features of selected internal diseases I. Collagen vascular / autoimmune diseases II. Endocrinopathies III. Disseminated infections

Criteria for diagnosis: Systemic Lupus Erythematosus 1. Malar rash 5. Arthritis 2. Discoid rash 6. Serositis 3. Photosensitivity 7. Renal disorder 4. Oral ulcers 8. Neurologic disorder 9. Hematologic disorder 10. Positive anti-nuclear antibody 11. Anti-dsDNA or anti-Smith antibody Need > 4 over any span of time for diagnosis:

Systemic Lupus Erythematosus malar erythema discoid plaques or psoriasiform erythema photosensitivity, alopecia, and mucosal ulcers Raynaud’s phenomenon periungual erythema

malar erythema

annular psoriasiform macules and patches

annular psoriasiform macules and patches

annular psoriasiform macules and patches

Periungual erythema

Criteria for diagnosis: Dermatomyositis 1. Symmetrical limb girdle weakness 2. Muscle biopsy evidence of inflammatory myonecrosis. 3. Elevated muscle enzymes (CPK, Aldolase, LDH). 4. Characteristic EMG features 5. Dermatological features Heliotrope with periorbital edema 1. Gottron’s sign - scaly dermatitis over dorsum of hands, extensor joint surfaces, face, upper torso 2. Definite : 3 criteria plus rash Probable : 2 criteria plus rash Possible : 1 criteria plus rash

Dermatomyositis Heliotrope erythema: Periungual erythema  periorbital purple/erythema and edema Gottron’s sign:  erythematous scaling macules and papules @ dorsa of the knuckles and elbows Periungual erythema

Heliotrope erythema

Heliotrope erythema

Gottron papules

Gottron papules Periungual erythema

Criteria for diagnosis: Progressive systemic sclerosis Major criteria: Proximal Scleroderma : Symmetrical thickening, tightening, induration of skin of digits and dorsal hands; may affect entire extremity and involve face and torso Minor criteria: 1. Sclerodactyly: skin changes (above) limited to digits 2. Digital pitted scars or loss of finger pad soft tissue 3. Basilar pulmonary fibrosis Diagnosis requires 1 major or 2 minor criteria

Progressive Systemic Sclerosis Scleroderma  Widespread or localized  Sclerodactyly = induration of digits  bird-like facies = pursed lips and bound-down skin of the nose (~beak-like appearance) Raynaud phenomenon Periungual erythema

Sclerodactyly

Sclerodermatous plaques

bird-like facies

Periungual erythema and hemorrhage

Vasculitis characterized by inflammation within or … characterized by inflammation within or around blood vessels Clinical presentation: depends on size and site of vessels involved solely cutaneous, systemic or combination  joints, kidneys, lungs, GI and nervous system

Cutaneous signs: Vasculitis Small vessel involvement (arterioles, venules, capillaries): Palpable purpura; petechiae, urticaria, pustules, vesicles, erythema multiforme Medium vessel involvement (mid-sized arteries and veins): Livedo reticularis, ulcers, nodules, digital infarcts

Causes: Vasculitis Idiopathic 50% of cases Blood disease Cryoglobulinemia Connective tissue disease Systemic LE, rheumatoid arthritis Sulphonamides, penicillin, serum sickness Drugs Hepatitis B, streptococci, Infections M. leprae, Rickettsia Neoplasia Lymphoma, leukemia Wegener’s granulomatosis, giant cell arteritis, polyarteritis nodosa Other

Palpable purpura

Palpable purpura

Livedo reticularis

Henoch-Schönlein purpura vasculitis with arthritis, abdominal pain, and hematuria mainly affects children often follows streptococcal infection

Henoch-Schönlein purpura

Henoch-Schönlein purpura

Diabetes Mellitus Acanthosis nigricans: Necrobiosis lipoidica:  brown velvety patches @ fold areas (esp. neck and axillae) Necrobiosis lipoidica:  atrophic patches with enlarging erythematous borders; legs most commonly affected Scleredema:  induration of the skin of the back and posterior neck.

Acanthosis Nigricans

Necrobiosis Lipoidica

Cutaneous features of other endocrinopathies Condition Cutaneous features Cushing’s syndrome Striae, hyperpigmentation, hypertrichosis (excessive levels of cortisol) Addison’s disease W areas of friction (adrenal insufficiency) Cool, dry, indurated skin; dull dry, coarse Hypothyroidism hair Moist warm skin, recurrent erythema, Hyperthyroidism alopecia, pretibial myxedema

Infective Endocarditis Infection of endocardium, most commonly due to St. aureus petechiae, splinter hemorrhages (linear red streaks under the nail) Osler nodes:  tender purpuric nodules on the finger pads and toes) Janeway lesions:  nontender purpuric macules of the palms and soles

tender nodules Nontender macules

Infective Endocarditis Osler nodes Janeway lesions Infective Endocarditis

Meningococcemia Symptoms: fever, headache, hemorrhagic rash Septicemia due to Neisseria meningitidis Symptoms: fever, headache, hemorrhagic rash  Purpura and associated gunmetal grey patches

Acute meningococcemia Acute meningococcemia. Large areas of purpura with central gunmetal-gray discoloration.

CUTANEOUS SIGNS INDICATIVE OF SYSTEMIC DISEASE

Erythema Nodosum Due to panniculitis (inflammation of the subcutaneous fat) deep, firm, and tender reddish-blue nodules, 1-5 cm diameter Most commonly at calves and shins

Erythema Nodosum associated with arthralgia and fever Tx: NSAIDS, po steroids

Causes of Erythema Nodosum Idiopathic About 20% of cases Streptococci, TB, leprosy, Yersinia, Mycoplasma, Rickettsia Bacterial Fungal Viral Coccidioidomycosis Cat-scratch fever Drugs Sulphonamides, oral contraceptives Inflammatory bowel disease, sarcoidosis, Behçet’s disease, malignancy (rare) Systemic diseases

Acanthosis nigricans Potential causes obesity Asymptomatic brown velvety plaques of coalescent papules Affects flexures - neck, axillae, groin Potential causes obesity endocrine disorders (acromegaly, insulin- resistant diabetes) Inherited GI malignancy

Pyoderma Gangrenosum rapidly expanding ulcer with purple undermined border, start as pustules Often affects legs Causes 50% idiopathic; 10% associated with ulcerative colitis;    Other associations: Crohn’s, chronic active hepatitis, rheumatoid arthritis, HIV, leukemia, myeloma

Acquired Ichthyosis If develops in adulthood, consider: Preamble: Ichthyosis is usually inherited and starts in infancy If develops in adulthood, consider:  underlying malignancy (e.g. Hodgkin’s disease),  essential fatty acid deficiency (e.g. due to malabsorption from intestinal by-pass or from lipid lowering drugs)

Generalized pruritus without an eruption Causes:  Idiopathic (‘senile’)  Iron deficiency  Liver disease  Malignancy (e.g. Hodgkin’s lymphoma)  Neurological disorders  Polycythemia  Renal failure  Thyroid dysfunction

Selected cutaneous signs associated with internal malignancies sudden-onset Acanthosis nigricans (GI) adult- onset Acquired ichthyosis (lymphoma) pyoderma gangrenosum (myeloma, leukemia) widespread intractable pruritus without rash (lymphoma)

Summary Cutaneous manifestations of common systemic diseases Cutaneous signs suggestive of systemic disease and internal malignancy