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

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

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

4. 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:

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

6. malar erythema

7. annular psoriasiform macules and patches

8. annular psoriasiform macules and patches

9. annular psoriasiform macules and patches

10. Periungual erythema

11. 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

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

13. Heliotrope erythema

14. Heliotrope erythema

15. Gottron papules

16. Gottron papules
Periungual erythema

17. 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

18. 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

19. Sclerodactyly

20. Sclerodermatous plaques

21. bird-like facies

22. Periungual erythema and hemorrhage

23. 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

24. 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

25. 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

26. Palpable purpura

27. Palpable purpura

28. Livedo reticularis

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

30. Henoch-Schönlein purpura

31. Henoch-Schönlein purpura

32. Diabetes Mellitus Acanthosis nigricans: Necrobiosis lipoidica:
 brown velvety 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.

33. Acanthosis Nigricans

34. Necrobiosis Lipoidica

35. 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

36. 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

37. tender nodules
Nontender macules

38. Infective Endocarditis
Osler nodes
Janeway lesions
Infective Endocarditis

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

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

42. CUTANEOUS SIGNS
INDICATIVE OF SYSTEMIC DISEASE

43. 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

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

45. 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

46. 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

48. 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

50. 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)

52. 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

53. 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)

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