1. Cutaneous Manifestations of Internal Disease Ronald Buckley, D.O. Dermatology Department Lakeview Medical Center Suffolk,Virginia April 02 2011

2. Course Objectives: • Cutaneous findings may provide valuable clues to the diagnosis of underlying internal disease. • During this presentation, a limited number of internal diseases manifestations on the skin will be reviewed.

3. Course Objectives • At the conclusion of this talk, the audience will recognize the cutaneous manifestations of internal diseases involving: integument disorders, blistering diseases, internal cancers, cardiovascular disease, pulmonary disease, rheumatic disease, gastrointestinal, and metabolic disease. • Goals • Help the primary care physician to establish the proper diagnosis and management. • Determine the need for referral to the appropriate specialist.

4. Common Benign Cutaneous Disorders Blistering Diseases Internal Cancers Cardiovascular Disease Pulmonary Disease Rheumatic Disease Gastrointestinal Disease Metabolic Disease Overview

5. Common Benign Cutaneous Disorders • Seborrheic Dermatitis • Chronic and common inflammatory disease. • Location: scalp, face, chest and intertriginous areas. • Clinical appearance: erythematous, often greasy, scaling patches and plaques favor hair bearing areas. Scalp pruritus is common. • Internal Association: HIV/AIDS and Langerhan Cell Histiocytosis (Letterer-Siwe, Hand Schuller-Christian and eosinophilic granuloma).

6. Seborrheic Dermatitis

7. Seborrheic Dermatitis

8. Common Benign Cutaneous Disorders • Seborrheic Dermatitis • Differential Diagnosis: eczema, psoriasis, tinea infection, zinc deficiency and lupus erythematosus. • Treatment: shampoos, sulfacetamide, azeleic acid, coal tar, topical steroids and topical or oral antifungal.

9. Tinea Facei

10. Common Benign Cutaneous Disorders • Seborrheic keratoses • Extremely common benign tumor. • Location: Anywhere but most commonly on the trunk. • Clinical appearance: warty plaques and “stuck on” appearance, “greasy” with pseudohorn cysts.

11. Seborrheic keratoses

12. Common Benign Cutaneous Disorders • Seborrheic keratoses • Internal Association: underlying adenocarcinoma of GI tract if they appear suddenly in great numbers (sign of Leser-Trelat). • Differential Diagnosis: Malignant Melanoma. • Treatment: reassurance, cryotherapy, curettage or excision.

13. Common Benign Cutaneous Disorders • Urticaria and Angioedema • Transient lesions most often triggered by medication (PCN, Sulfa, ASA) or food (nuts, eggs, milk, shellfish), and less so by infection. • Location: Localized, regional, or generalized. • Clinical appearance: edematous papules and plaques with oval, annular, polycyclic, serpiginous, and bizarre shapes.

14. Urticaria

15. Urticaria

16. Common Benign Cutaneous Disorders • Urticaria and Angioedema • Internal Association: Urticarial vasculitis-type II immune complex reaction. • Urticarial plaques that persists for 24-72 hrs. • Associated with purpura, scaling, and hyperpigmentation. • Differential diagnosis: erythema multiforme, SLE, bullous pemphigoid, mastocytosis. • Treatment: elimination of known causes, antihistamines, systemic steroids, sulfasalazine and cyclosporine.

17. Urticarial Vasculitis

18. Angioedema

19. Common Benign Cutaneous Disorders • Erythema multiforme • Relatively common- hypersensitive, acute and often recurrent inflammatory process. • Location: backs of hands and feet, extensor surfaces of forearms and arms and less commonly on the trunk. • Clinical Appearance: targetoid, morbilliform, plaques, vesicles or bullae.

20. Erythema multiforme

21. Common Benign Cutaneous Disorders • Erythema multiforme • Internal Association: HSV, mycoplasma, connective tissue diseases and drugs. • Differential diagnosis: urticaria, drug eruption bullous pemphigoid. • Treatment: oral antiviral for herpes infection; discontinuation of offending medication; oral prednisone and supportive care.

22. Common Benign Cutaneous Disorders • Vitiligo • Type of acquired leukoderma. Autoimmune disease. • Location: focal (periorificially -mouth ,orbits, vagina, anus), segmental and generalized. • Clinical appearance: Depigmented macules and patches.

23. Vitiligo

24. Vitiligo

25. Common Benign Cutaneous Disorders • Vitiligo • Internal Association: thyroid dz, diabetes mellitus, pernicious anemia or Addison’s dz. • Differential Diagnosis: pityriasis alba, tinea versicolor, postinflammatory hypopigmentation, hypopigmented mycosis fungoides. • Treatment: sunscreen, topical steroids, tacrolimus or pimecrolimus, phototherapy, skin grafting and depigmentation.

26. Common Benign Cutaneous Disorders • Erythema nodosum • Most common type of panniculitis. • Location: lower legs (most common in females), knees, arms, rarely face and neck. • Clinical Appearance: painful, indurated, tender, red to violaceous nodules. • Internal Association: Infectious ( streptococcal pharyngitis), drug sensitivity (sulfonamide,oral contraceptives), inflammatory bowel dz and sarcoidosis.

27. Erythema Nodousm

28. Erythema Nodosum

29. Common Benign Cutaneous Disorders • Erythema nodosum • Differential diagnosis: nodular vasculitis and other panniculitis. • Treatment: elimination of known triggers, bed rest, NSAIDs, colchicine, and supersaturated iodide.

30. Life Threatening Cutaneous Disorder • Exfoliative Dermatitis (Erythroderma) • Potentially a life-threatening reaction pattern involving the skin. • Location: generalized . • Clinical appearance: generalized and confluent redness and scaling of the skin with associated systemic “toxicity”, generalized lymphadenopathy, pruritus, malaise, chills, and fever. • Causes: most commonly are preexisting skin diseases: • Psoriasis, atopic dermatitis and drug hypersensitivity.

31. Exfoliative dermatitis

32. Exfoliative dermatitis

33. Life Threatening Cutaneous Disorder • Exfoliative Dermatitis (Erythroderma) • Internal Association: Cutaneous T Cell Lymphoma (less commonly), leukemia and pityriasis rubra pilaris. • Differential diagnosis: lichen planus, pemphigus foliaceus, ichthyosiform erythroderma, acute graft-versus-host disease. • Treatment: hospitalized in single room with attention to the patient need for temperature control. Water baths with bath oils followed by application of bland emollients.

34. Life Threatening Cutaneous Disorder • Exfoliative Dermatitis (Erythroderma) • Treatment: Oral and topical corticosteroids for remission induction only. • Supportive (cardiac, fluid, electrolyte, protein replacement).

35. Blistering Disorders • Pemphigus vulgaris • Serious acute or chronic debilitating blistering autoimmune disease of the skin and mucous membrane. Often fatal unless treated with immunosuppresive agents. • Location: mouth or generalized. Predilection for the scalp, face chest, axillae, groin, umbilicus. • Clinical appearance: Vesicles and bullae, flaccid, easily ruptured, and weeping, arising on normal skin. Extensive erosions that bleed easily with crusting. Nikolsky’s sign.

36. Blistering Disorders • Pemphigus Vulgaris • Diagnosis: Bx of the skin and mucous membrane, DIF (IgG/C3) and circulating auto-antibodies(IgG). • DDX: BP, Steven-Johnson, EBA • Tx: Immunosuppressive agents, systemic corticosteroids, plasmapheresis, topical corticosteroids and antibiotics, rituximab and IVIg.

37. Pemphigus Vulgaris

38. Pemphigus Vulgaris

39. Blistering Disorders • Bullous pemphigoid • Chronic autoimmune mediated bullous eruption in patients over 60 yrs of age. • Location: Generalized or localized and randomly distributed. Rarely involve oral mucosa. • Clinical appearance: Large tense firm-topped bullae. May arise in normal or erythematous skin and often pruritic.

40. Bullous Pemphigoid

41. Blistering Disorders • Bullous pemphigoid • Diagnosis: Clinical, confirmed by histopathology and immunopathology (IgG at DEJ) • Differential Diagnosis: bullous SLE, EBA, cicatricial pemphigoid and DH. • Treatment: excellent prognosis with treatment; topical and systemic corticosteroids, TCN, niacinamide, steroid sparing immunosuppressants.

42. Blistering Disorders • Dermatitis herpetiformis (DH) • Intensely pruritic chronic and recurrent eruption. • Location: symmetrical groups on the elbows, knees, scalp, and buttocks. • Clinical appearance: tiny vesicles, papules, and urticarial wheals.

43. Dermatitis Herpetiformis

44. Blistering Disorders • Dermatitis herpetiformis (DH) • Internal association: small-bowel malabsorption. Gluten-sensitive enteropathy. • Diagnosis: Clinical, confirmed by histopathology and immunopathology. • Circulating IgA antibodies (antiendomysial antibodies) in 70% pts. • Differential Diagnosis: linear IgA dermatosis, BP, contact dermatitis and bullous LE. • Treatment: dapsone, sulfapyridine, gluten-free diet.

45. Blistering Disorders • Epidermolysis bullosa acquisita (EBA) • Rare autoimmune bullous disease. • Location: hands, feet, elbows, knees and mucous membrane. • Clinical appearance: skin fragility, milia, scarring alopecia, and nail dystrophy, tense blisters on inflammatory or noninflammatory base.

46. Epidermolysis bullosa acquisita

47. Epidermolysis bullosa acquisita

48. Blistering Disorders • Epidermolysis bullosa acquisita (EBA) • Diagnosis: Clinical, confirmed by histopathology and immunopathology. • Differential Diagnosis: bullous pemphigoid bullous LE. • Treatment: Poor response to topical and systemic therapy. Cyclosporine and high dose intravenous immunoglobulins may be effective.

49. Skin Disease and Internal Cancer • Cutaneous metastases • Occur in less that 5% of patients with metastatic cancer. • Generally reflect the most prevalent cancer in the general population (breast, lung, or GI tract) • Clinical appearance: skin-colored to violaceous nodules in close proximity to the primary neoplasm. • Location: most commonly seen on the head, neck and trunk. • DDx: cyst, adnexal tumor, neurofibroma and lipoma

50. Metastatic Carcinoma