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Welcome to Dermatology Disneyland

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Welcome to Dermatology Disneyland!

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Drugs N’ Derm

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Urticaria Intensely pruritic Circumscribed, raised, erythematous with central pallor Can enlarge and coalesce, usually disappears over a few hours IgE (Type I): Antibiotics (especially penicillins, cephalosporins, and sulfonamides) Local anesthetic agents Radiocontrast media Foreign proteins (blood products and gamma-globulin) Latex: localized and generalized Incidence increases with exposure ACE inhibitor-induced urticaria is likely due to changes in the vascular response to bradykinin in the skin and mucous membranes

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Urticaria

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Drug-induced exanthems Exanthems, morbilliform and macular and papular eruptions Start dependent areas and generalize, often with mucus membrane erythema. Blood eosinophilia may be present but isn’t reliable Morbilliform eruptions can be the presenting signs of more serious reactions such as toxic epidermal necrolysis (TEN), hypersensitivity syndrome, and serum sickness Onset: usually within 2 weeks of drug start, within days re-exposure Chemically related compounds--phenytoin and carbamazepine can have cross-reactions

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Morbilliform: begin in dependent areas and generalize

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Hypersensitivity vasculitis The American College of Rheumatology: 5 criteria for the classification of hypersensitivity vasculitis in a patient with vasculitis Age >16 years Use of a possible offending drug in temporal relation to the symptoms Palpable purpura Maculopapular rash Biopsy of a skin lesion showing neutrophils around an arteriole or venule

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Hypersensitivity vasculitis Clinical findings: palpable purpura and/or petechiae include fever, urticaria, arthralgias, lymphadenopathy, low serum complement levels, and an elevated erythrocyte sedimentation rate. Variable time length

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%%%

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Leukocytic vasculitis: Raised purpura. Can occur with any vasculitic syndrome or collagen vascular dz.

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Exfoliative dermatitis & Erythroderma Chronic erythema and scale involving greater than 50 percent of the body surface area. Common etiologies include drugs, primary skin disease (atopic dermatitis, psoriasis), and malignancy (especially lymphoreticular malignancy and cutaneous T-cell lymphoma). Drugs are responsible for 10 percent of erythrodermas; implicated drugs include penicillins, barbiturates, gold, arsenic, and mercury Drug-induced erythroderma begins with a generalized eczema or morbilliform erythema accompanied by some irritation that increases steadily in severity. Eventually total body erythema with significant edema occurs. Manage like a burn

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Erythroderma: Erythema and >50% BSA

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Drug induced exfoliation

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Stevens-Johnson syndrome and toxic epidermal necrolysis TEN (toxic epidermal necrolysis): discrete red macules (SJS) but with larger confluent areas of necrosis Appears to be spectrum of dz <10% BSA = SJS >30% BSA = TEN Erythema multiforme major (frequently synonym for SJS), most likely different condition Acute eruption Target lesions Histology often reveals infectious cause (Herpes virus or Mycoplasma) Benign clinical course Widely disseminated purpuric macules and blisters and prominent involvement of the trunk and face are likely to have SJS (usually drug induced)

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Erythema Multiforme

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Start 1 to 3 wks after start (more rapid with re-challenge) Patients with systemic lupus erythematosus (SLE), HLA phenotype B12, and HIV infection have an increased incidence of these disorders. Mucosal involvement: SJS and TEN 90% of cases Painful crusts and erosions on any surface Most common: oral covity, conjunctivae and genital mucosa Ocular: can have scar tissue, keratitis and even blindness Differential includes: Exfoliative erythroderma Paraneoplastic pemphigus Acute exanthematous pustulosis Staph scalded skin syndrome Skin biopsies to exclude these disorders: don’t see full thickness epidermal necrosis Monitor in burn unit. Stevens-Johnson syndrome and toxic epidermal necrolysis

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Toxic Epidermal Necrolysis

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Hypersensitivity syndrome Severe idiosyncratic reaction rash and fever Often associated hepatitis, arthralgias, lymphadenopathy, or hematologic abnormalities Antiepileptic agents (phenytoin, carbamazepine and phenobarbital) and the sulfonamides: most frequently implicated Overall risk of hypersensitivity to phenytoin: 1:1000 to 1:10,000 Hard to distinguish clinically from serum sickness or vasculitis clinically 2 to 6 wks after drug first used (later than other skin reactions) Eruption presents with erythematous follicular papules and pustules Bullae and purpura can also be seen Fever and rash are present in 87 percent Lymphadenopathy in 75 percent Hepatitis in 51 percent Interstitial nephritis in 11 percent Hematologic abnormalities (eosinophilia and circulating atypical monocytes) in 30 percent Recovery is usually complete, but the reaction can be severe enough to require oral corticosteroids

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Fixed drug eruption Acutely by erythematous and edematous plaques with a grayish center or frank bullae, and chronically by a dark postinflammatory pigmentation Favored sites include the mouth (lips and tongue), genitalia, face, and acral areas. Features: Postinflammatory hyperpigmentation Recurrence exactly the same site with drug reexposure Common: phenolphthalein (laxatives), tetracyclines, barbiturates, sulfonamides, NSAIDs, and salicylates

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Fixed Drug Eruption

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Drug-induced lupus Can exascerbate underlying lupus or induce lupus in pre-disposed Or drug-induced lupus: Penicillin, sulfonamides, and anticonvulsant drugs might exacerbate underlying lupus, current opinion suggests that these patients had lupus and were receiving appropriate medications Similar to spontaneous lupus Lupus-like syndrome: Procainamide hydralazine

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Drug Induced Lupus

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Cutaneous Presentation of Malignancy

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Dermatologic Paraneoplastic Syndromes Includes direct involvement of the skin with tumor as well as the remote effects of cancer Mechanism unclear: may be caused by tumor production or depletion of biologically active hormones or growth factors. Possibly, tumor-induced host immunologic response—for example, antigen cross-reactivity between tumor and skin—may cause skin changes

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Dermatologic Paraneoplastic Syndromes Early diagnosis Age appropriate cancer screens Certain dermatologic manifestations are more closely associated with certain types of cancers Some genetic syndromes (ie Gardner’s, Peutz-Jeghers, NF) associated with derm findings and malignancy.

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Acanthosis Nigricans Velvety, verrucous hyperpigmentation of the neck, axilla, groin, and mucosal membranes, including the lips, periocular area, and anus. Can be benign (insulin resistance) Most are adenocarcinomas: intra-abdominal, 70%-90%; gastric, 50%-60% Age over 40 The lesions often regress with successful treatment of the underlying tumor

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Tripe palms Rugose, velvety palms; may be associated with AN Lung CA most often; gastric CA second in frequency, especially with AN

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Acquired ichthyosis Diffuse rhomboidal scales on trunk and extensor surfaces Hodgkin's lymphoma, 70%-80%

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Sign of Lesar-Trélat Diffuse acute eruption of seborrheic keratoses Multiple (>100) small to medium seborrheic keratoses Associated with AN in 20% of cases Associated with gastrointestinal CAs, breast CAs, and lymphoproliferative CAs Also associated with normal aging

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Dermatomyositis Muscle weakness; photoaccentuated dermatitis Periorbital heliotrope rash; flat-topped papules over knuckles, Erythema, telangiectasia, atrophy, Gottron’s papules Multiple associated malignancies have been reported; increased ovarian CA in women

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Bazex's syndrome Hyperkeratosis paraneoplastica Acral hyperkeratotic papulosquamous lesions, onychodystrophy Squamous cell carcinomas of the oropharynx, larynx, bronchi, esophagus

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Paraneoplastic pemphigus Painful erythematous lesions with blistering; mucous membrane ulcerations Pruritic, polymorphous lesions, bullae, papules-plaques on trunk, oral areas Lymphoproliferative: 42% non-Hodgkin, 29% CLL

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Erythema gyratum repens Concentric rings on trunk and proximal extremities; may have pruritus Rapidly progressing located on trunk, proximal parts of extremities Characteristic swirling Lung cancer, bronchial CA most frequent (32%)

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Necrolytic migratory erythema Erosive erythematous rash, stomatitis Migratory erythematous macules or papules in annular configuration on face, abdomen, thighs, perianal and oral areas Glucagonoma; Pancreatic alpha-cell tumor

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Sweet's syndrome High fever; malaise, arthralgias; skin rash Red nodules or plaques, fever, dermal neutrophilic infiltrates Acute myelogenous leukemia (also seen with infection)

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Pyoderma gangrenosum Discrete ulcers with undermined borders AML most frequent, multiple myeloma next; solid tumors rare

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Acquired hypertrichosis lanuginosa Increased hair on face or other areas Men: lung first, colorectal second Women: colorectal first, lung or breast second

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Other associations Herpes Zoster Migratory thrombophlebitis: Firm, linear, cordlike lesions involving superficial vessels…associated with visceral cancers, prostate CAs Pruritus: Excoriations; associated with lymphoma and myeloproliferative disease Erythroderma: Diffuse erythema associated with lymphoma

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Common etiologies include drugs, primary skin disease (atopic dermatitis, psoriasis), and malignanc more Common etiologies include drugs, primary skin disease (atopic dermatitis, psoriasis), and malignancy (especially lymphoreticular malignancy and cutaneous ... less