derm, drug eruptions

7/28/2019 Derm, Drug Eruptions

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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.Downloaded from: Dermatology (on 29 June 2006 07:55 PM)

2005 Elsevier


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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. Downloaded from: Dermatology (on 29 June 2006 07:55 PM) 2005 Elsevier


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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)

Downloaded from: Dermatology (on 29 June 2006 07:55 PM)

2005 Elsevier


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Erythema Multiforme (EM)

This has many causes, drug eruption is oneetiology

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.


2005 Elsevier


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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 2mucous 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 befatal


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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; canrapidly turn into TEN (hrs)

TEN: Extremely rapid course. Evolves withinhours. 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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2005 Elsevier


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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)

2005 Elsevier


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Figure 21.7 Severe conjunctival erosions and exudate in SJS

secondary to trimethoprim-sulfamethoxazole therapy.


2005 Elsevier


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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) 2005 Elsevier


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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) 2005 Elsevier


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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 anarea of er thematous skin.


2005 Elsevier


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TEN


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Urticaria

Has many causes! Pressure, exercise, food,

temperature, and drug

Transient lesion (


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Angioedema

severe form of urticaria

involving dermis andsubcutaneous swelling which

can affect airway, mucosa,

and bowels.

Can be from food, medication,

latex allergy


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Angioedema

Can occur simultaneouslywith urticaria

Angioedema withouturticaria can also occur

Drug reactionC1 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 Reactions

Management 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 inhSeen in lymphoproliferative disease, esp.

multiple myeloma, Waldenstroms, B celllymphoma, CLL

Type 2

autoantibodies (IgG1) against C1 inh

Associated with SLE, RA, Sjogrens


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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 muscleinflammation

Characteristic Skin Manifestations:

Heliotrope Rash Gottrons papules/sign

Poikiloderma (atrophy, telangectasia, and pigmentaryalteration)

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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Gottrons Papules

Pathogmonic for Dermatomyositis

Erythematous-violaceous scaly papules over

dorsal IP joints, elbows, or knees Gottrons 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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Gottrons papules


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Figure 44.4 Gottron's sign with violaceous poikiloderma over the

knuckles.


2005 Elsevier


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Figure 44.2 Violaceous poikiloderma of the face, plus thin plaques

on the elbows (Gottrons sign) that are sometimes misdiagnosed as

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

2005 Elsevier


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Figure 44.1 Violaceous poikiloderma of the face. Heliotrope also

noted.


2005 Elsevier


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Dermatomyositis

Up to 25% are associated with underlying

malignancy

Ovarian cancer is overrepresented inwomen

Patients with new diagnosis need cancer

screening at diagnosis and yearly


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Scleroderma

Disorder characterized by fibrosis of connectivetissue, increased collagen deposition, and vascularalterations.

Localized disease without systemic manifestationsis called morphea or localized scleroderma

Systemic disease with skin manifestations is calledsystemic 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).


2005 Elsevier


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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 rashwhen 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

nasolabial folds.Downloaded from: Dermatology (on 29 June 2006 08:28 PM)

2005 Elsevier


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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.


2005 Elsevier


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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

and crusting of the borders.Downloaded from: Dermatology (on 29 June 2006 08:28 PM)

2005 Elsevier


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Discoid Lupus Erythematous

(DLE) Most scarring and chronic form of cutaneous

lupus

Discoid shaped plaques with white scale, withtime, lesions become atrophic

Can lead to scarring alopecia

Few patients meet criteria for SLE

Treat with intralesional or topical steroids, sunavoidance, plaquenil if severe or large areasinvolved


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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.Downloaded from: Dermatology (on 29 June 2006 08:28 PM)

2005 Elsevier


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Figure 43.10 Chronic cutaneous lupus erythematosus (CCLE)

discoid lesion.


2005 Elsevier


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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 caf 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-celllymphoma

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 paperwrinkling

Serpiginous or annular

Non-specific rash, can

resemble psoriasis oreczema

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!

derm, drug eruptions

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