drug eruptions, author unknown
TRANSCRIPT
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Rotator Lecture VI
Drug Eruptions, CTD, NF, MF
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Exanthematous Drug Eruptions
• Most common manifestation of drug reactions
• Presents as erythematous macules and papules coalescing into diffuse erythema
• Skin may peel as rash is resolving
• Most common causes include sulfa, PCN, and PCN derivatives
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Figure 23.1 Exanthematous drug eruptions. Numerous pink papules on the trunk due to a cephalosporin (A). Confluence of lesions on
the trunk (B) and annular plaques on the forehead (C) secondary to phenobarbital.
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Figure 23.1 Exanthematous drug eruptions. Numerous pink papules on the trunk due to a cephalosporin (A). Confluence of lesions on
the trunk (B) and annular plaques on the forehead (C) secondary to phenobarbital.
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Usually worst on LE due to orthostatic pressure.
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Fixed Drug Eruption• Occurs in the same place each time a
patient is challenged with a particular drug
• Round or oval lesion with an ash gray to slate blue colored center, may have bullae
• Can have 1 lesion or multiple
• Common causes include laxatives, NSAIDs, sulfa drugs, tetracyclines
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Figure 23.11 Fixed drug eruptions. Well-demarcated erythematous (A) to violet-brown plaques that can develop a detached epidermis
Responsible drug was phenophthalein (A)
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Erythema Multiforme (EM)
• This has many causes, drug eruption is one etiology
• Erythematous target-like lesions• Minor variant does not require
hospitalization– Usually a reaction to HSV infection
• Major variant (Stevens-Johnson) requires hospitalization and immediate treatment
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Figure 21.1 Phenotypic variety in EM. D classic target lesions on the palms.
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Stevens Johnsons Syndrome (SJS) and Toxic Epidermal Necrosis
(TEN)
• SJS and TEN always caused by a drug• More severe than EM• Involves mucosa• SJS arbitrarily defined as involving at least 2
mucous membranes and having at least 10% body surface area involved
• TEN is worst end of spectrum with more severe cutaneous and mucosal manifestations and can be fatal
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SJS and TEN
• Common causes include antiepileptics, sulfa drugs• More severe than EM• SJS: Rapid course, large sheets of necrotic skin,
can involve mucosa, evolves within days; can rapidly turn into TEN (hrs)
• TEN: Extremely rapid course. Evolves within hours. Can be fatal! Treat patient in burn unit, administer IV Ig, plasma pheresis
• Oral/systemic steroids have not been able improve mortality (can increase susceptibility to infection)
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Figure 21.6 Denuded and crusted lesions of the lips with minimal cutaneous lesions in a child with SJS secondary to antibiotic
therapy.Downloaded from: Dermatology (on 29 June 2006 07:55 PM)
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Figure 21.7 Severe conjunctival erosions and exudate in SJS secondary to trimethoprim-sulfamethoxazole therapy.
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Figure 22.6 Stevens-Johnson syndrome (SJS) versus SJS-TEN overlap. In addition to mucosal involvement and widespread erythematous papules, there are small areas of epidermal
detachment (arrows). Because the latter involve 10% body surface area, the patient is classified as having SJS.Downloaded from: Dermatology (on 29 June 2006 07:55 PM)
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Figure 22.5 Clinical features of toxic epidermal necrolysis (TEN). A Detachment of large sheets of necrolytic epidermis (>30% body
surface area), leading to extensive areas of denuded skin. B Hemorrhagic crusts with mucosal involvement. C Epidermal
detachment of palmar skin.Downloaded from: Dermatology (on 29 June 2006 07:55 PM)
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Figure 22.4 Cutaneous features of toxic epidermal necrolysis (TEN). A Characteristic dusky-red color of the early macular
eruption in TEN. Lesions with this color often progress to full-blown necrolytic lesions with dermo-epidermal detachment. B Positive Nikolsky sign: epidermal detachment reproduced by mechanical
pressure on an area of erythematous skin.Downloaded from: Dermatology (on 29 June 2006 07:55 PM)
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TEN
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Urticaria
• Has many causes! Pressure, exercise, food, temperature, and drug
• Transient lesion (<24 hours), new ones can form with continued contact
• Resolve without scarring
• Remove offending agent(s), administer anti-histamines
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Angioedema
• severe form of urticaria involving dermis and subcutaneous swelling which can affect airway, mucosa, and bowels.
• Can be from food, medication, latex allergy
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Angioedema
• Can occur simultaneously with urticaria
• Angioedema without urticaria can also occur– Drug reaction– C1 esterase inhibitor
deficiency
JAAD 2002; 46: 645-57.
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Angioedema: Drug Reactions
ACE Inhibitors • Often orofacial angioedema• Urticaria/angioedema is believed to result
from the inhibition of endogenous kininase• Can occur up to 1 yr after starting med
NSAIDs
Aspirin
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Angioedema: Drug ReactionsManagement
• Withdrawal of drug
• Antihistamines, corticosteroids
• Epinephrine may be needed if airway in trouble or very severe
• Report of FFP used in refractory case (to above and IVIg, CSA)
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Hereditary Angioedema• Autosomal dominant; with incomplete penetrance• 1:150,000• Mutations in one copy of the gene for C1 inhibitor
– Type 1: reduced levels of C1 inh (85% of cases)
– Type 2: functionally deficient C1 inh (15% of cases)
• C1inh deficiency allows activation of the C1 – generation of bradykinin
– subsequent consumption of complement leads to low levels of C4 in the serum
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Hereditary Angioedema
• Trauma can precipitate attacks
• Attacks last 48-72 hrs– Laryngeal edema– Abdominal pain
• NO WHEALS (ie NO URTICARIA)
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Hereditary Angioedema
Fitz 6th ed p 1132
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Acquired Angioedema
Type 1• C1 fixed by anti-idiotypic antibodies causes
consumption of C1 inh– Seen in lymphoproliferative disease, esp.
multiple myeloma, Waldenstroms, B cell lymphoma, CLL
Type 2• autoantibodies (IgG1) against C1 inh
– Associated with SLE, RA, Sjogren’s
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Angioedema (only) work-up• Medications:
– Avoid estrogens
• FH• C4 : BEST SCREEN
– Screens both hereditary and acquired C1 inhibitory deficiency
• C1q– Low in acquired C1 inh def.
• C1 inh assay– Amount: type 1 deficiency
– Function: type 2 deficiency
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Hereditary Angioedema: Rx
• C1 inh concentrate of FFP– For emergencies
• Tranexamic acid (IV)– FDA approved for hemophilia– antifibrinolytic agent: competitively inhibits the
activation of plasminogen to plasmin
• Danazol, Stanozolol: treatment of choice
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Acquired Angioedema: Rx
• Secondary to lymphoproliferative disease– Stanozolol– Danazol
• Secondary to anti-C1Inh autoantibodies– Respond to glucocorticoids
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Dermatomyositis• Combination of skin and striated muscle
inflammation• Characteristic Skin Manifestations:
– Heliotrope Rash – Gottron’s papules/sign– Poikiloderma (atrophy, telangectasia, and pigmentary
alteration)
• Muscle Manifestations– Symmetric proximal muscle weakness– Elevation of skeletal muscle enzymes (CPK, aldolase)– EMG, muscle biopsy, and MRI can also be used to
confirm myositis
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Heliotrope: periorbital edema with a lightly violaceous hue
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Gottron’s Papules
• Pathogmonic for Dermatomyositis• Erythematous-violaceous scaly papules
over dorsal IP joints, elbows, or knees• Gottron’s sign are patches or plaques of the
same color in the same distribution• Photosensitivity is the proposed etiology• Associated with proximal nail fold atrophy
and telangiectasia
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Gottron’s papules
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Figure 44.4 Gottron's sign with violaceous poikiloderma over the knuckles.
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Figure 44.2 Violaceous poikiloderma of the face, plus thin plaques on the elbows (Gottron’s sign) that are sometimes misdiagnosed as
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Figure 44.1 Violaceous poikiloderma of the face. Heliotrope also noted.
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Dermatomyositis
• Up to 25% are associated with underlying malignancy
• Ovarian cancer is overrepresented in women
• Patient’s with new diagnosis need cancer screening at diagnosis and yearly
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Scleroderma
• Disorder characterized by fibrosis of connective tissue, increased collagen deposition, and vascular alterations.
• Localized disease without systemic manifestations is called “morphea” or “localized scleroderma”
• Systemic disease with skin manifestations is called “systemic scleroderma”– Subsets of this are CREST and systemic sclerosis
• ANA is not helpful in diagnosis
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Localized form of morphea: ‘en coup de sabre’
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Limited Systemic Sclerosis: CREST
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Sclerodactyly seen in CREST
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Figure 45.3 Mat telangiectasias in a patient with systemic sclerosis (scleroderma).
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Progressive Systemic Sclerosis
• Skin thickening is more widespread and proximal
• Can be severe and rapidly fatal
• Both CREST and PSS can causes renal disease and pulmonary sclerosis
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Cutaneous Lupus
• ACUTE: Typical photosensitive malar rash when acute– Highly associated with systemic LE (almost
100%)
• SUBACUTE: This variant is psoriasiform or papulosquamous– ~50% of these patients will meet criteria for
SLE
• CHRONIC: ie Discoid Lupus– Most patients (85-90% never develop systemic
lupus)
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Figure 43.4 Acute cutaneous lupus (ACLE) lesions in a butterfly distribution on the face of a young woman. Note sparing of
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Figure 43.5 Acute cutaneous lupus (ACLE). The patient shown in this photo had ACLE lesions on the arms as well as the face.
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Figure 43.7 Subacute cutaneous lupus (SCLE) lesions of the sun-exposed aspects of the upper arm. Note the annular configuration
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Discoid Lupus Erythematous (DLE)
• Most scarring and chronic form of cutaneous lupus
• Discoid shaped plaques with white scale, with time, lesions become atrophic
• Can lead to scarring alopecia• Few patients meet criteria for SLE• Treat with intralesional or topical steroids, sun
avoidance, plaquenil if severe or large areas involved
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Figure 43.9 Chronic cutaneous lupus erythematosus (CCLE) with discoid lesions. The ear is a common site of involvement. Note the central depigmentation, scarring and peripheral hyperpigmentation.
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Figure 43.10 Chronic cutaneous lupus erythematosus (CCLE) discoid lesion.
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Neurofibromatosis • Type 1 (vonRecklinghousen) is more common that
Type 2• Autosomal dominant inheritance in half of cases,
other half are spontaneous• Hereditary form has variable penetrance; can be
associated with mental retardation • Some Criteria: 2 or more neurofibromas, 6 or
more café au lait macules, Lisch nodules in the eyes, Axillary or inguinal freckles (Crows sign)
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Mycosis Fungoides (MF)
• Most common type of cutaneous T-cell lymphoma
• NOT A FUNGAL DISEASE!• Most common in middle-aged white men• Occurs in patch and plaque stages • Asymmetrical distribution of lesions • Treat with steroids, UVB, nitrogen mustard,
PUVA, methotrexate, retinoids, interferons
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Patch vs. Plaque Stages of MF
• Flat• Fine white scale• Erythematous • ‘Cigarette paper’
wrinkling• Serpiginous or annular• Non-specific rash, can
resemble psoriasis or eczema
• Localized
• Red to violaceous nodules
• Associated with lymphadenopathy
• Alopecia
• Hyperkeratosis of palms and soles
• Widespread
• Lesions can become ulcerated
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Thank You!