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Cutaneous Manifestations of Internal Disease

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

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

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 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

51 Metastatic Carcinoma

52 Skin Disease and Internal Cancer
Mammary Paget’s disease Unilateral breast cancer-nearly always associated with underlying intraductal carcinoma. Clinical appearance: eczematous plaque of the nipple and areola with exudate that persists for longer than a few weeks. Resistant to topical therapy. Differential Diagnosis: allergic or irritant contact dermatitis, psoriasis, BCC, Bowens dz. Treatment: Referral to oncologist, surgery, radiation, photodynamic therapy.

53 Paget’s Disease

54 Skin Disease and Internal Cancer
Extramammary Paget’s Disease Neoplasm of the anogenital and axillary skin. Histologically and clinically similar to Paget’s dz of the breast. Often represents an intraepidermal extension of primary adenocarcinoma of underlying adnexal (apocrine) carcinoma or underlying cancer of GI tract or GU tract. Location: vulva, scrotum, penis, perianal, perineal, axilla,umbilicus and sternum. Clinical appearance: erythematous plaque +/- scaling, crusting, and exudation. Borders sharply defined.

55 Extramammary Paget’s Disease

56 Skin Disease and Internal Cancer
Extramammary Paget’s Disease. Differential Diagnosis: eczematous dermatitis, intertriginous Candida infection, tinea corporis, erythrasma, Bowen’s dx, HPV induced intraepithelial neoplasia, superficial spreading melanoma. Treatment: surgical excision.

57 Skin Disease and Internal Cancer
Acanthosis nigricans most likely triggered by factors that stimulate epidermal keratinocyte and dermal fibroblast proliferation. benign form- the factor likely insulin or an insulin-like growth factor malignant AN- stimulating factor secreted either by the tumor or in response to the tumor.

58 Acanthosis Nigricans

59 Acanthosis Nigricans

60 Skin Disease and Internal Cancer
Acanthosis Nigricans Location: groin, axillae, neck. Malignant form has sudden onset and more extensive distribution- face and dorsal and palmar surfaces of hands . Clinical appearance: smooth, velvet-like, hyperkeratotic plaques of intertriginous areas. Internal association: Adenocarcinoma – GI, lung, breast. Most common causes are obesity, insulin-resistant diabetes and medications.

61 Tripe Palms

62 Skin Disease and Internal Cancer
Acanthosis Nigricans Differential diagnosis: confluent and reticulated papillomatosis, Dowling-Degos dz. Treatment: treatment of underlying disorder, including removal of malignant tumor.

63 Skin Disease and Internal Cancer
Gardner’s syndrome Autosomal dominant cancer syndrome Characterized by: Colonic polyposis Osteomas (maxilla, mandible, skull) Scoliosis Epidermoid cysts Soft-tissue tumors (fibromas, desmoid tumors, lipomas) Pigmented ocular fundus lesions Adenocarcinoma of colon develops in 60% of pts by the age of 40.

64 Epidermal Inclusion Cyst

65 Skin Disease and Internal Cancer
Muir-Torre Syndrome Autosomal dominant cancer syndrome. Characterized by at least one sebaceous tumor (adenoma, sebaceoma, epithelioma, or carcinoma) and one internal neoplasms, usually colorectal(47%), GU(21%), breast CA(12%) and hematologic(9%) Clinical appearance: small asymptomatic papules or nodules that resembles cysts or benign growths to waxy papules located mainly of the face, trunk and scalp.

66 Sebaceous Adenoma

67 Sebaceous Neoplasms

68 Skin Disease and Internal Cancer
Cowden’s Syndrome Autosomal dominant. Mutations in tumor suppressor gene PTEN Characterized by: Multiple tricholemmomas (resemble warts) around the mouth, nose and ears. Breast and thyroid cancer Fibrocystic disease of the breast Thyroid adenoma Mental retardation

69 Skin Disease and Internal Cancer
Hirsutism Appearance of excessive coarse, male-type pattern, hair in woman. Associated androgen excess (adrenal or ovarian tumor). Hypertrichosis Excessive growth of vellus hairs in any hair-bearing areas Associated with malignancy, metabolic disorders or medications (minoxidil and cyclosporine).

70 Hirsutism

71 Skin Disease and Internal Cancer
Sweet’s syndrome (acute neutrophilic dermatosis) Strong association with acute myelocytic or myelomonocytic leukemia. Clinical appearance: abrupt onset of tender or painful reddened plaques or nodules occasionally with vesicles, bullae or pustules on the face, extremities, and trunk usually in middle-aged women.

72 Sweet’s Syndrome (acute febrile neutrophilic dermatosis)

73 Sweet’s Syndrome

74 Skin Disease and Internal Cancer
Sweet’s syndrome (acute neutrophilic dermatosis) Associated systemic symptoms: fever, peripheral leukocytosis, arthralgias, myalgias and conjunctivitis. Differential diagnosis: erythema multiforme, SLE, deep fungal infection, pyoderma gangrenosum, cutaneous metastases. Treatment: systemic corticosteroids, NSAIDs and dapsone.

75 Skin Disease and Internal Cancer
Amyloidosis May be a sign of multiple myeloma. Clinical: waxy, smooth, shiny, flat-topped or spherical papules, nodules or plaques. “Pinch Purpura” Location: midface, tongue, scalp, body folds, axillae, umbilicus, anogenital area. Treatment: no effective therapy, chemotherapy and stem cell transplantation.

76 Primary systemic amyloidosis

77 Macroglossia (Amyloidosis)

78 Purpura (Amyloidosis)

79 Skin Disease and Internal Cancer
Dermatomyositis An inflammatory systemic disease; Characterized: proximal muscle weakness, photosensitivity, violaceous (heliotrope) inflammatory changes of eyelids and periorbital area, papules and plaques of hands, elbows, and knees (Gottron’s papules). Elevated creatine kinase or aldolase level, positive Jo-1 antibody, and EKG changes.

80 Heliotrope erythema

81 Gottron’s papules

82 Dermatomyositis

83 Skin Disease and Internal Cancer
Dermatomyositis Other features: scaly, telangiectatic plaques with atrophy and hypopigmentation (poikiloderma) on face, neck, trunk , extremities, malar erythema and nail abnormalities (periungal telangiectases and cuticular hypertrophy).

84 Dermatomyositis

85 Skin Disease and Internal Cancer
Dermatomyositis Diagnosis: requires muscle bx, electromyogram, measurement of muscle enzymes (aldolase, creatine kinase, transaminases). Internal association: Adenocarcinoma of breast, GI tract or lung in adults. Differential diagnosis: SLE, photosensitive drug eruption. Treatment: systemic corticosteroids, MTX, immunosuppressants and TNF alpha inhibitors.

86 Skin Disease and Internal Cancer
Paraneoplastic pemphigus Autoimmune disease with clinical and histological features of EM and PV. Clinical appearance: intractable stomatitis and blisters , conjunctival reactions, polymorphous skin lesions. Location: oral mucosa, trunk, extremities.

87 Paraneoplastic pemphigus

88 Skin Disease and Internal Cancer
Paraneoplastic pemphigus Internal association: non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, thymoma. Diagnosis: histopathology and immunopathology. Treatment: based on underlying dz.

89 Skin Disease and Internal Cancer
Erythema gyratum repens Rare by most distinctive skin eruption Clinical appearance: reddened concentric bands in a wood grain or whorled pattern. Internal association: lung, breast, cervical and GI cancers. Treatment: removal of cancer clears the eruption.

90 Erythema gyratum repens

91 Skin Disease and Cardiovascular Disease
Multiple Lentigines LEOPARD Syndrome (Moynahan’s) Lentigines Electrocardiographic changes Ocular telorism Pulmonary stenosis Abnormal genitalia Retarded growth Deafness


93 Skin Disease and Cardiovascular Disease
Multiple Lentigines NAME Nevi Atrial myxoma Myxoid neurofibromas Ephelides

94 Skin Disease and Cardiovascular Disease
Multiple Lentigines LAMB Syndrome Lentigines Atrial myxoma Mucocutaneous myxomas Blue nevi

95 Skin Disease and Cardiovascular Disease
Pseudoxanthoma elasticum (PXE) An inherited or acquired defect of elastic tissue. Mutations in the gene ABCC6 on chromosome 16 have been linked to PXE. Clinical appearance: yellow cobblestone lesions over redundant skin folds in flexural location arranged in linear distribution – “plucked chicken”. Location: Neck and axillae most common sites.

96 Pseudoxanthoma Elasticum (PXE)

97 Angioid Streaks

98 Skin Disease and Cardiovascular Disease
Pseudoxanthoma elasticum (PXE) Internal association: HTN, peripheral vascular and coronary dz, retinal and GI hemorrhage, strokes and angioid streaks. Differential diagnosis: cutis laxa, Ehlers-Danlos syndrome. Treatment: no definitive therapy.

99 Skin Disease and Cardiovascular Disease
Ehlers-Danlos syndrome An inherited defect of collagen tissue at least eleven types. Clinical appearance: hyperextensibility, hypermobility, skin fragility, “fish-mouth” scars. Internal association: MVP, blue sclerae, aneurysm, aortic dissection, hernias, angina, GI bleeding and peripheral vascular dz. Treatment: protection of skin and treatment of systemic findings.

100 Ehlers-Danlos Syndrome

101 Ehlers-Danlos Syndrome

102 Skin Disease and Pulmonary Disease
Sarcoidosis Chronic multisystem granulomatous inflammation. Clinical appearance: red to violaceous plaques of the nose (lupus pernio), midfacial papules, annular plaques, nodules or plaques on trunk and extremities. Erythema nodosum-mt common cutaneous manifestation. Higher prevalence in women and African Americans. Differential diagnosis: trichoepitheliomas, rosacea, granuloma annulare. Treatment: systemic corticosteroids, antimalarials, MTX, thalidomide and TNF alpha inhibitors.

103 Sarcoidosis

104 Sarcoidosis

105 Skin Disease and Rheumatic Disease
Psoriatic arthritis A distinct form of arthritis with negative rheumaotoid factor. HLA-B27 genotype in 50% of affected patients. Clinical appearance: five types: Asymmetric arthritis-most common type with “sausage” fingers and toes Symmetric arthritis Distal interphalangeal joint disease Arthritis mutilans Ankylosing spondylitis

106 Psoriatic Arthritis

107 Psoriatic Arthritis

108 Skin Disease and Rheumatic Disease
Psoriatic arthritis Differential diagnosis: rheumatoid arthritis. Treatment: Biologic agents, NSAID’s, antimalarials, MTX, retinoids, cyclosporine.

109 Skin Disease and Rheumatic Disease
Lupus erythematosus A multisystem autoimmune photosensitive dermatosis. Clinical forms: 1. DLE- localized to head or neck with scarring plaques usually negative ANA. 2. SCLE-annular plaques on trunk and arms with positive ANA, Ro(SS-A), La(SS-B). 3. SLE-malar erythema, photosensitivity, oral ulcers, discoid plaques, alopecia, positive- ANA, dsDNA, Ro(SS-A), La(SS-B), sm.

110 Discoid Lupus Erythematosus

111 Systemic Lupus Erythematosus (SLE)

112 Skin Disease and Rheumatic Disease
Lupus erythematosus. Clinical forms: 4. Neonatal LE- noticed in first month, photosensitive, papulosquamous and annular patterns, congenital heart block 50% of cases. Maternal passage of antibodies- Ro, La, U 1-RNP, Antiphospholipids. 5. Drug-Induced LE- rash uncommon, ANA, ssDNA, antihistone positive. Procainamide, Hydralazine, Isoniazid. Symptoms clear with stopping the med. Treatment: Sun protection, steroids, dapsone and immunosuppressants.

113 Neonatal LE

114 Skin Disease and Rheumatic Disease
Reiter’s syndrome Triad: urethritis, conjunctivitis, and oligoarthritis. Circinate balanitis-vesicles and crusted plaques. Keratoderma blennorrhagicum-erythematous pusutles and papules on palms and soles. Sacroiliitis-present 50% of pt (HLA-B27). Treatment: topical corticosteroids for skin dz.

115 Skin Disease and Gastrointestinal Disease
Hepatitis C infection association: Leukocytoclastic vasculitis Cutaneous B-cell lymphoma Cryoglobulinemia Pruritus Porphyria cutanea tarda Urticaria Prurigo nodularis Lichen planus

116 Leukocytoclastic Vasculitis

117 Skin Disease and Gastrointestinal Disease
Peutz-Jeghers Syndrome Characterized: lentigines on skin and mucosa-lips, buccal mucosa, periorbital region, dorsal of fingers and soles. Associated: benign polyps (hamartomas) of small intestine with low malignant potential. DDx: LEOPARD syndrome, Carney complex and Cronkhite-Canada syndrome Tx: regular and routine endoscopy and symptomatic treatment.

118 Peutz-Jeghers Syndrome

119 Skin Disease and Gastrointestinal Disease
Pyoderma gangrenosum Neutrophilic dermatosis with painful ulcers with boggy, undermined edges and a border of gray or purple pigmentation. Associated: inflammatory bowel dz, rheumatoid arthritis or paraproteinemia usually IgA gammopathy. Differential diagnosis: infection, vasculitis, factitious disorder. Treatment: systemic, intralesional and topical corticosteroids; cyclosporine, infliximab and immunosuppressants.

120 Pyoderma Gangrenosum

121 Skin Disease and Metabolic Disease
Porphyrias A group of inherited or acquired blistering disorders of heme biosynthetic pathway. Porphyria cutanea tarda (PCT) Most common porphyria. Hepatic porphyria (acquired/sporadic). Deficiency uroporphyrinogen decarboxylase. Accumulation of by products in urine/serum.

122 Porphyria Cutanae Tarda (PCT)

123 Porphyria Cutanae Tarda (PCT)

124 Skin Disease and Metabolic Disease
Porphyrias Porphyria cutanae tarda (PCT) Precipitating factors: alcohol ingestion, estrogen administration, dinitrochlorobenzene, carbon, tetrachloride, dialysis, hepatitis B or C infection. Clinical appearance: photosensitivity, skin fragility, bullae, erosions of sun-exposed skin, milia and hypertrichosis. Differential diagnosis: bullous SLE, EBA, pseudoporphyria. Treatment: phlebotomy, antimalarials.

125 Test Exfoliative dermatitis Dermatitis herpetiformis
Acanthosis nigricans Gardners’s syndrome Muir-Torre Syndrome Cowden’s Syndrome Erythema nodosum Erythema Multiforme Amyloidosis Sweet’s Syndrome A. HSV/Mycoplasma B. Strep. Pharyngitis C. Psoriasis, Eczema, drug D. Gluten sensitive enteropathy E. Obesity-Insulin resist. DM F. Colonic Polyposis G. Colorectal/GU CA (Sebaceous tumors) H. Breast & Thyroid CA (Tricholemmomas) I . Multiple Myeloma J. AML

126 References 1. Longshore S, Tomecki K. The Cleveland clinic disease management project. Skin signs of systemic disease. 2002;1-8. www. 2. Von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31:535. 3. Poole S. Fenske NA. Cutaneous markers of internal malignancy. I, II J Am Acad Dermatol. 1993;28:1,147. 4. Fitzpatrick T, Johnson R et al. Color atlas and synposis of Clinical Dermatology 2nd edition Habif T. Clinical Dermatology: A color guide to diagnosis and treatment. 3rd edition Arndt K, Leboit P et al. Cutaneous medicine and surgery: an integrated program in dermatology WWW. (digital images) WWW.

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