drug eruptions, author unknown

Rotator Lecture VI

Drug Eruptions, CTD, NF, MF

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

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.

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

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

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

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

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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

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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

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

Angioedema

• severe form of urticaria involving dermis and subcutaneous swelling which can affect airway, mucosa, and bowels.

• Can be from food, medication, latex allergy

Angioedema

• Can occur simultaneously with urticaria

• Angioedema without urticaria can also occur– Drug reaction– C1 esterase inhibitor

deficiency

JAAD 2002; 46: 645-57.

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

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)

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

Hereditary Angioedema

• Trauma can precipitate attacks

• Attacks last 48-72 hrs– Laryngeal edema– Abdominal pain

• NO WHEALS (ie NO URTICARIA)

Hereditary Angioedema

Fitz 6th ed p 1132

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

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

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

Acquired Angioedema: Rx

• Secondary to lymphoproliferative disease– Stanozolol– Danazol

• Secondary to anti-C1Inh autoantibodies– Respond to glucocorticoids

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

Heliotrope: periorbital edema with a lightly violaceous hue

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

Gottron’s papules

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

psoriasis.Downloaded from: Dermatology (on 29 June 2006 09:20 PM)

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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

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

Localized form of morphea: ‘en coup de sabre’

Limited Systemic Sclerosis: CREST

Sclerodactyly seen in CREST

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

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)

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

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)

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

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

Thank You!