skin clues to internal disease · pathogenesis ? viral etiology focus on human herpesvirus-7...

Medical

Dermatology

• Pruritus & Urticaria

• Drug Eruptions

• Other Common Rashes

• Recognize & Refer

Nishit Patel, M.D.

CONFLICTS OF INTEREST

• No Relevant Conflicts

Special Thanks to Leigh Ann Scalf, MD

OBJECTIVES

• Learn to diagnose and manage pruritus without a primary

eruption

• Diagnosis and treatment of urticaria

• Identify features of common drug eruptions

• Identify drug rashes that constitute dermatologic emergencies

OVERVIEW

Pruritus = “Itching”

Urticaria = “Hives”

PRURITUS WITHOUTPRIMARY LESIONS

In other words…”just itching and scratching.”

So, now what??

COMMON PRESENTATION

Butterfly area over scapulae often spared because the

patient cannot reach the area to scratch.

Beware: some patients are very flexible and CAN reach

this area!!

“BY THE BOOK”

The million dollar work-up can be

found in any text book

But….

PRACTICAL PRURITUS WORK UP

CBC (anemia)

LFT (Hepatic dysfunction)

BUN/Cr (Renal dysfunction)

TSH (Hypothyroidism)

ANA (Lupus)

CXR (Cancer)

All “age appropriate” cancer screenings

Get a complete “ROS”

URTICARIA

GROUPING OF URTICARIA

• Acute Urticaria (<6 wks)

• Cause

• 50% idiopathic/unknown

• 40% Upper respiratory tract

infections

• 9% drug reaction

• 1% food related

• Prognosis – Excellent, usually resolves

within days to weeks

• Chronic Urticaria (>6 wks)

• Cause

• 60% - idiopathic/unknown,

autoimmune, infection related

• 35% physical urticaria

• 5% urticarial vasculitis

• Prognosis – 50% of patients with

chronic urticaria will resolve in 1 year.

Can be very difficult to manage.

URTICARIA / ANGIOEDEMA

Pruritic wheals

Individual

lesions

disappear

within 24 hours.

DERMATOGRAPHISM

https://upload.wikimedia.org/wikipedia/commons/thumb/4/42/Dermatographic_urticaria.jpg/1200px-

Dermatographic_urticaria.jpg

May be associated with:

Angioedema

Anaphylaxis with

bronchospasm,

laryngospasm, or

hypotension

URTICARIA / ANGIOEDEMA

If the patient gives a history of anaphylaxis (throat swelling, difficulty breathing):

Give Rx for Epi-Pen (Twin Ject) and “Emergency Plan”

Refer to Allergist

URTICARIA / ANGIOEDEMA

URTICARIA / ANGIOEDEMA

Immunologic

Most commonly associated with penicillin and beta-

lactam antibiotics

Nonimmunologic

Aspirin and NSAIDS are the most common causes.

Also caused by radiocontrast. (*Pre-testing does NOT

exclude the possibility of an anaphylactoid reaction to radiocontrast.)

ACE inhibitors can cause angioedema

African Americans at nearly 5

times greater risk than caucasians

Lisinopril and enalapril > captopril

Blockade of kininase II by ACE

inhibitors may increase the tissue

kinin levels, thus enhancing

urticarial reactions and

angioedema.

URTICARIA / ANGIOEDEMA

OTHER “URTICARIAS”

• Physical Urticaria

• Urticarial Vasculitis

“EMPHASIS ON TREATMENT…”URTICARIA

• Anti-Histamines (non/low-sedating), over-the-counter

• Loratidine (Claritin), Cetirizine (Zyrtec), Fexofenadine (Allegra), Levocetirizine

(Xyzal)

• Anti-Histamines (non/low-sedating), prescription only

• Desloratidine (Clarinex) 5mg daily (AM or PM)

• Anti-Histamines (sedating, use at night only)

• Diaphenhydramine (Benadryl) 25mg (at bedtime)

• *Hydroxyzine (Atarax) 10mg/25mg/50mg (at bedtime)

• *Doxepin 10mg/25mg (at bedtime)

• Additional Tx Considerations:

• *Anti-Histamines (H2- Blockers), Prednison, *Montelukast (Singulair),

Omalizumab (Xolair)

* off label usage

EMPHASIZE TRIGGER AVOIDANCE

• Avoid NSAIDs (non-steroidal anti-inflammatory

medicationsAspirin, Ibuprofen (Motrin), Aleve (naproxen),

Meloxicam, Celebrex, etc.

• Avoid triggers of mast-cell degranulation (histamine release)

• Medications = Opioids (narcotic pain medications), contrast dyes

(radiology imaging), anticholinergic medications, polymyxin B sulfate (

in topical antibiotics)

• Heat/friction

• Alcohol

OTHER WORKUP TO CONSIDER

• CBC

• CMP

• ESR

• ANA

• TSH

• IgE

• C3, C4

• C1-Inh

(qualitative/quantitative)

• C1q

• Anti-C1q

• CH50

PEARLS

1) Pruritus without primary lesions should be worked up to rule out any underlying etiology.

2) Urticaria: Individual lesions disappear within 24 hours.

3) Immunologic urticaria: Most commonly associated with penicillin and beta-lactam antibiotics

4) Non-immunologic urticaria: Aspirin and NSAIDS are the most common causes.

5) Antihistamines are the mainstay of treatment for urticaria.

Drug Eruptions

DRUG ERUPTIONS, OVERVIEW

Extremely diverse

Almost any drug may be capable of

producing a reaction.

A certain drug may also cause several

different reaction patterns in different

patients.

IN GENERAL…DRUG ERUPTIONS

Most occur within days to weeks after beginning

the offending agent

Occasionally a reaction begins after long-term use

of a particular drug

**MORBILLIFORM (AKA: EXANTHEM-LIKE, MACULAR AND PAPULAR, SCARLETINIFORM) ERUPTIONS ARE THE MOST FREQUENT OF

ALL CUTANEOUS REACTIONS TO DRUGS

EXANTHEMS

“MORBILLIFORM” OR

“SCARLETINIFORM” REACTIONS

Pruritus common

Usually occur with in first 2 weeks of

treatment

Usually start proximally (groin/axillae),

then generalize within 1-2 days

PATHOGENESIS

NON-IMMUNOLOGIC

IMMUNOLOGIC

*Drug reactions :

-not simply drug allergy

-may result from variations in drug metabolism, immune status, coexistent diseases, and other co-administered medications.

EXANTHEM-LIKE ERUPTIONS

Most common culprits:

Penicillins

Cephalosporins

Sulfonamides

Carbamazepine

Hydantoins

Allopurinol

Gold

“EMPHASIS ON TREATMENT…”

“Simple exanthems”(skin only!)

Supportive care

stop offending med, topical steroids, antihistamines

FIXED DRUG ERUPTION

FIXED DRUG ERUPTION

Adverse reaction to an ingested drug

Usually solitary

Plaque, bulla, or erosion

Upon rechallenge, FDE occurs at identical site within hours of ingestion

FIXED DRUG ERUPTION

Usually asymptomatic

May be pruritic or burning

Painful if eroded

Post-inflammatory pigmentary alteration (PIPA) remains between flares – usually hyperpigmentation.

MOST COMMONLY IMPLICATED DRUGS:

Phenolphthalein

Antimicrobials Tetracyclines

Sulfonamides

Psychoactive agents

Anti-inflammatory agents

OCPs

Quinine

Pseudoephedrine (Sudafed)

FIXED DRUG ERUPTION

Treatment:

identify and stop offending drug

Non-eroded: potent topical steroid

Eroded: bacitracin or silvadene

PIPA (dermal melanin) does NOT

respond to hydroquinone therapy

GOOD RASH GONE BAD!

Occasionally, exanthem-like eruptions are

associated with:

Interstitial nephritis

Hepatitis

Lymphadenopathy

So, don’t forget to do a

thorough history and physical!

1) Drug reactions are DIVERSE.

2) Certain drugs are more likely to produce certain reactions.

3) The most common drug reaction is a moribilliformeruption.

4) Simple “skin-only” exanthems require supportive care…stop offending medication, topical steroids, antihistamines.

5) There can be systemic involvement. *Do a thorough history and physical!!

6) Fixed drug eruptions recur in the same location upon re-exposure to the offending agent

“GOOD RASH” PEARLS

OTHER COMMON RASHES

Image from: https://www.merckmanuals.com/-/media/manual/professional/images/4812-pityriasis-rosea-herald-patch-public-

health-image-library-high.jpg?la=en&thn=0

• A self-limited papulosquamous eruption that is

occasionally pruritic

• Seen mainly in adolescents and young adults, favoring the

trunk and proximal extremities

• Individual lesions are usually oval in shape and their long axis

is oriented along the lines of cleavage

• Less common variants include inverse, vesicular, purpuric and

pustular

PITYRIASIS ROSEA

Pathogenesis

? Viral etiology

Focus on human herpesvirus-7 (HHV-7) and, less so, on HHV-6

Some studies have shown no difference in prevalence of DNA from HHV-6 or HHV-7 in pts

w PR

Support for viral etiology: prodromal symptoms experienced by some, clustering of cases,

and almost complete absence of recurrent episodes, suggesting immunologic defense against

infectious agent

Epidemiology

Female > male

Affects otherwise healthy adolescents and young adults

Typical eruption lasts 6-8 weeks, then resolves spontaneously

May occasionally last > 5 months

? Slight seasonal variation

PITYRIASIS ROSEA

“Herald Patch” Large skin- to pink- to salmon-colored patch or plaque with slightly raised

advancing margin Center – fine scaling (like other lesions) Margin - larger, more obvious trailing collarette of scale with the free edge pointing

inwards

Often on trunk, precedes other lesions by hours to days Seen in ~50% of cases

~5% of pts experience a mild prodrome

PITYRIASIS ROSEA - CLINICAL

Other lesions

Similar to herald patch but smaller

Rapidly appear, usually on trunk and proximal extremities

Long axis following Langer's lines of cleavage “Christmas tree” pattern on back

More papular and hyperpigmentedin pts w/ skin of color

May be pustular initially

Face, palms and soles usually spared

PITYRIASIS ROSEA - CLINICAL

Pruritus in ~25% of pts

Atypical forms of pityriasis rosea

Inverse - axillae and inguinal areas;

sometimes the face

More common in younger children and in

those with darkly pigmented skin

Other: urticarial, erythema multiforme-

like, vesicular, pustular and purpuric

variants

PITYRIASIS ROSEA - CLINICAL

Treatment

Patient education and reassurance

Pruritis

Counterirritant antipruritic lotions

Low- to medium-strength topical corticosteroids

Severe cases

UVB – reduces severity of PR but not duration or pruritus

Antihistamines

Short course oral steroids

PITYRIASIS ROSEA - CLINICAL

ERYTHEMA ANNULARECENTRIFUGUM (EAC)

• Erythema Annulare Centrifugum (EAC)

• Applies to a broad spectrum of clinical findings, “default” diagnosis

• Peak age: 40s

• No known gender difference

• Can last days-decades

• Possibly represents a reaction pattern or hypersensitivity to one of

many Ag’s

• Dermatophytes, candida, other fungi, viruses (pox, EBV, VZV,

HIV), drugs, food, pregnancy, AI endocrinopathies,

hypereosinophilic syndrome, neoplasms

CLINICAL

• Initial lesions: firm, pink papules that expand centrifugally & develop central clearing

• Can grow to >6cm over 1-2 wks

• Superficial gyrate erythema:

• Minimally elevated

• Central trailing scale (sometimes vesicles @ outer edge)

• +/- pruritus

• Deep gyrate erythema:

• Advancing edge elevated & usually no associated scale

• Majority are non-pruritic

• No scarring, but can get PIH

• Lesions last weeks-months

• No systemic sx’s

• Rare on palms, soles, scalp, mucous membranes

EAC

DIFFERENTIAL AND TREATMENT

• DDx: tinea corporis, annular psoriasis, annular urticaria,

allergic urticarial eruption, cutaneous lymphoid hyperplasia,

lymphoma cutis, linear IgA bullous dz, Sjogren’s, LE

• TREATMENT:

• Resolves if underlying d/o is responsible & treated

• Topical steroid to advancing edge

• Tacrolimus, calcipotriol, oral metronidazole, etanercept

STASIS DERMATITIS

• Disease of adults

• Eruption of lower extremities

• Can see concomitant edema, brownish hyperpigmentation

• Most common site is medial malleolus

• Pathogenesis:

• Venous htn →distension of capillaries → incr permeability → fluid, proteins, RBCs in tissue → protein (fibrin) around blood vessels inhibit O2 diffusion; activation of PMNs & Mφ; release of inflamm mediators; plt accum (focal thrombosis) → fibrosis & tissue remodeling

• Treatment: leg elevation, support stockings, topical steroids, Aluminum acetate compresses

• Higher risk of ACD sensitization with topical antibiotic application

STASIS DERMATITIS

• Complicating pathogenic factors: contact (58%-86%) and irritant dermatitis

• Lipodermatosclerosis- progressive induration occurs over years-inverted wine bottle appearance

• Tx: compression stockings/ bandages; exercise calf muscles; venous surgery; wound dressings, topical steroids and emollients

STASIS DERMATITIS

• Erythematous to skin-colored, sometimes purple–brown or yellowish, waxy indurated nodules or plaques with classic peaud’orange

• Painful, pruritic

• Location: anterolateral aspect of the lower legs or feet

• Non-pitting

• Hypertrichosis and hyperhidrosis

LOCALIZED (PRETIBIAL) MYXEDEMA: CLINICAL

LOCALIZED (PRETIBIAL) MYXEDEMA

• Induration of the shins due to mucin deposition

• Mucin production stimulated by a serum factor unrelated to

thyroid-stimulating Ig’s

• Associated w/ hyperthyroidism

• Especially Graves disease (1-5% of pts w/ Grave’s)

• W/ exopthalmous (25%)

• May also appear in hypothyroid state following treatment of

Graves

DDx LSC, hypertrophic LP, lymphedema, obesity-associated

lymphedematous mucinosis, and elephantiasis

Tx Corticosteroids (topically or intralesionally)

Especially if symptomatic

Other: plasmapheresis, gradient pneumatic compression, IVIg, and octreotide

Treating the hyperthyroidism does NOT improve the cutaneous lesions

May clear spontaneously (after an average of 3.5 years)

LOCALIZED (PRETIBIAL) MYXEDEMA

RECOGNIZE & REFER

Images from:

• https://www.mayoclinic.org/-/media/kcms/gbs/patient-consumer/images/2013/08/26/10/41/ds00722_im02463_r7_bullouspemphigoidthu_jpg.jpg

• https://jamanetwork.com/data/Journals/DERM/11776/dob40010f1.png

• https://www.dermnetnz.org/topics/bullous-pemphigoid/

BULLOUS PEMPHIGOID

• Most common subepidermal blistering

disease

• Affects elderly, rarely children

• 90 yo’s have 300X risk of developing

compared to 60 yo’s

• Men>women

Images from: Dermatology by Jean L., M.D. Bolognia, Joseph Jorizzo, Ronald Rapini C.V. Mosby (June 1, 2003)

BULLOUS PEMPHIGOID: CLINICAL FEATURES

• Early non-bullous phase

• Nonspecific, pruritus, eczematous, excoriated eruptions, urticarial lesions

• Weeks to months

• May be the only signs of the disease

• Bullous phase

• Erythematous urticarial lesions + tense vesicles/bullae on

normal/erythematous skin

• Symmetrical, predominately on flexural areas and lower trunk

• May form vegetating plaques in intertriginous areas

• Blisters resolve with PIPA, and milia rarely

• Oral involvement in 10-30%

Images from:

• https://www.facingacne.com/wp-content/uploads/2012/01/Pemphigus-vulgaris.jpg

• https://i.pinimg.com/originals/3f/54/b4/3f54b4e8e3e78d5c4e03b7e3d7fbaeac.jpg

PEMPHIGUS FOLIACEUS

Images from: https://www.dermquest.com/imagelibrary/large/10559-IMG_9023.JPG

PEMPHIGUS VULGARIS & FOLIACEUS

• Pemphigus = autoimmune disease of IgG antibodies against keratinocyte

cell surface

• Results in loss of cell-cell adhesion of keratinocytes acantholysis

intraepidermal blisters

• P. vulgaris and P. foliaceus

• Mean age: 50-60 y/o

• Men = women

• 0.76 to 5 per 1,000,000 new cases per year

• Higher in Jewish and Hispanic descendants of the conversos (SW USA)

• 16 to 32 per 1,000,000

• P. vulgaris is more common than P. foliaceus

• Except in Brazil, Finland, and Tunisia

REFERENCES

Habif: Clinical Dermatology, 4th ed. 2004 Mosby, Inc.

www.dartmouth.edu

Dermatology by Jean L., M.D. Bolognia, Joseph Jorizzo, Ronald Rapini C.V. Mosby (June 1, 2003)

Contact & Occupational Dermatology by James G. Marks, et al (January 15, 2002)

www.aad.org

Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology by Klauss Wolff, Richard. A. Johnson, Richard Suurmond

Fitzpatrick's Dermatology in General Medicine by Irwin M., Md. Freedberg (Editor), Arthur Z. Eisen (Editor), Klaus Wolff (Editor), K. Frank Austen (Editor), Lowell A. Goldsmith (Editor), Stephen I. Katz (Editor), Thomas B. Fitzpatrick (Editor)