Presentation on theme: "Cutaneous Manifestations of Internal Disease"— Presentation transcript:
1Cutaneous Manifestations of Internal Disease Ronald Buckley, D.O.Dermatology DepartmentLakeview Medical CenterSuffolk,VirginiaApril
2Course 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.
3Course ObjectivesAt 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.GoalsHelp the primary care physician to establish the proper diagnosis and management.Determine the need for referral to the appropriate specialist.
5Common Benign Cutaneous Disorders Seborrheic DermatitisChronic 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).
10Common Benign Cutaneous Disorders Seborrheic keratosesExtremely common benign tumor.Location: Anywhere but most commonly on the trunk.Clinical appearance: warty plaques and “stuck on” appearance, “greasy” with pseudohorn cysts.
12Common Benign Cutaneous Disorders Seborrheic keratosesInternal 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.
13Common Benign Cutaneous Disorders Urticaria and AngioedemaTransient 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.
16Common Benign Cutaneous Disorders Urticaria and AngioedemaInternal 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.
19Common Benign Cutaneous Disorders Erythema multiformeRelatively 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.
26Common Benign Cutaneous Disorders Erythema nodosumMost 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.
29Common Benign Cutaneous Disorders Erythema nodosumDifferential diagnosis: nodular vasculitis and other panniculitis.Treatment: elimination of known triggers, bed rest, NSAIDs, colchicine, and supersaturated iodide.
30Life 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.
33Life 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.
34Life Threatening Cutaneous Disorder Exfoliative Dermatitis (Erythroderma)Treatment: Oral and topical corticosteroids for remission induction only.Supportive (cardiac, fluid, electrolyte, protein replacement).
35Blistering 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.
36Blistering Disorders Pemphigus Vulgaris Diagnosis: Bx of the skin and mucous membrane, DIF (IgG/C3) and circulating auto-antibodies(IgG).DDX: BP, Steven-Johnson, EBATx: Immunosuppressive agents, systemic corticosteroids, plasmapheresis, topical corticosteroids and antibiotics, rituximab and IVIg.
39Blistering 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.
41Blistering 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.
42Blistering 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.
48Blistering 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.
49Skin Disease and Internal Cancer Cutaneous metastasesOccur 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
52Skin Disease and Internal Cancer Mammary Paget’s diseaseUnilateral 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.
54Skin Disease and Internal Cancer Extramammary Paget’s DiseaseNeoplasm 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.
57Skin Disease and Internal Cancer Acanthosis nigricansmost likely triggered by factors that stimulate epidermal keratinocyte and dermal fibroblast proliferation.benign form- the factor likely insulin or an insulin-like growth factormalignant AN- stimulating factor secreted either by the tumor or in response to the tumor.
60Skin Disease and Internal Cancer Acanthosis NigricansLocation: 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.
62Skin Disease and Internal Cancer Acanthosis NigricansDifferential diagnosis: confluent and reticulated papillomatosis, Dowling-Degos dz.Treatment: treatment of underlying disorder, including removal of malignant tumor.
63Skin Disease and Internal Cancer Gardner’s syndromeAutosomal dominant cancer syndromeCharacterized by:Colonic polyposisOsteomas (maxilla, mandible, skull)ScoliosisEpidermoid cystsSoft-tissue tumors (fibromas, desmoid tumors, lipomas)Pigmented ocular fundus lesionsAdenocarcinoma of colon develops in 60% of pts by the age of 40.
65Skin Disease and Internal Cancer Muir-Torre SyndromeAutosomal 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.
68Skin Disease and Internal Cancer Cowden’s SyndromeAutosomal dominant.Mutations in tumor suppressor gene PTENCharacterized by:Multiple tricholemmomas (resemble warts) around the mouth, nose and ears.Breast and thyroid cancerFibrocystic disease of the breastThyroid adenomaMental retardation
69Skin Disease and Internal Cancer HirsutismAppearance of excessive coarse, male-type pattern, hair in woman.Associated androgen excess (adrenal or ovarian tumor).HypertrichosisExcessive growth of vellus hairs in any hair-bearing areasAssociated with malignancy, metabolic disorders or medications (minoxidil and cyclosporine).
71Skin 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.
74Skin 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.
75Skin Disease and Internal Cancer AmyloidosisMay 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.
79Skin Disease and Internal Cancer DermatomyositisAn 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.
83Skin Disease and Internal Cancer DermatomyositisOther features: scaly, telangiectatic plaques with atrophy and hypopigmentation (poikiloderma) on face, neck, trunk , extremities, malar erythema and nail abnormalities (periungal telangiectases and cuticular hypertrophy).
85Skin Disease and Internal Cancer DermatomyositisDiagnosis: 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.
86Skin Disease and Internal Cancer Paraneoplastic pemphigusAutoimmune 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.
88Skin Disease and Internal Cancer Paraneoplastic pemphigusInternal association: non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, thymoma.Diagnosis: histopathology and immunopathology.Treatment: based on underlying dz.
89Skin Disease and Internal Cancer Erythema gyratum repensRare by most distinctive skin eruptionClinical 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.
95Skin 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.
98Skin 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.
99Skin Disease and Cardiovascular Disease Ehlers-Danlos syndromeAn 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.
102Skin Disease and Pulmonary Disease SarcoidosisChronic 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.
105Skin Disease and Rheumatic Disease Psoriatic arthritisA 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 toesSymmetric arthritisDistal interphalangeal joint diseaseArthritis mutilansAnkylosing spondylitis
109Skin Disease and Rheumatic Disease Lupus erythematosusA 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.
114Skin Disease and Rheumatic Disease Reiter’s syndromeTriad: 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.
115Skin Disease and Gastrointestinal Disease Hepatitis C infection association:Leukocytoclastic vasculitisCutaneous B-cell lymphomaCryoglobulinemiaPruritusPorphyria cutanea tardaUrticariaPrurigo nodularisLichen planus
117Skin Disease and Gastrointestinal Disease Peutz-Jeghers SyndromeCharacterized: 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 syndromeTx: regular and routine endoscopy and symptomatic treatment.
119Skin Disease and Gastrointestinal Disease Pyoderma gangrenosumNeutrophilic 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.
121Skin Disease and Metabolic Disease PorphyriasA 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.
124Skin Disease and Metabolic Disease PorphyriasPorphyria 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.
125Test Exfoliative dermatitis Dermatitis herpetiformis Acanthosis nigricansGardners’s syndromeMuir-Torre SyndromeCowden’s SyndromeErythema nodosumErythema MultiformeAmyloidosisSweet’s SyndromeA. HSV/MycoplasmaB. Strep. PharyngitisC. Psoriasis, Eczema, drugD. Gluten sensitive enteropathyE. Obesity-Insulin resist. DMF. Colonic PolyposisG. Colorectal/GU CA (Sebaceous tumors)H. Breast & Thyroid CA (Tricholemmomas)I . Multiple MyelomaJ. AML
126References1. Longshore S, Tomecki K. The Cleveland clinic disease management project. Skin signs of systemic disease. 2002;1-8. www. Clevelandclinicmeded.com/diseasemanagement/dermatology/skinsigns2. 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 editionHabif T. Clinical Dermatology: A color guide to diagnosis and treatment. 3rd editionArndt K, Leboit P et al. Cutaneous medicine and surgery: an integrated program in dermatologyWWW. Dermnet.com (digital images)WWW. Dermatlas.org