Ulcers - ASCCP

Ulcers

Aruna Venkatesan, MD

Associate Chief of Dermatology

Director of Genital Dermatology Clinic

Santa Clara Valley Medical Center (SCVMC)

Associate Professor of Dermatology, Affiliated

Stanford University

Disclosures

No financial relationships or conflict of interest to disclose

Learning Objectives

At the end of this lecture, the participant will gain knowledge on the:

• Definition of an ulcer

• Differential diagnosis of an ulcer

• Evaluation of ulcers

• Treatment strategies for ulcers

Recommended References

• Pipkin C. Erosive Diseases of the Vulva. Dermatol Clin. 2010 Oct;28(4):737-52.

• Bandow GD. Diagnosis and Management of Vulvar Ulcers. Dermatol Clin. 2010 Oct;28(4):753-64.

• Black M et al. Obstetric and Gynecologic Dermatology, 3rd Edition. Elsevier Limited, 2008.

• Edwards L and PJ Lynch, eds. Genital Dermatology Atlas, 2nd Edition. Philadelphia: Lippincott Williams & Wilkins, 2011.

Outline

• An exam finding not a diagnosis

• Ulcer vs. erosion

• Differential diagnosis

• Approach to evaluation• Physical exam• Other diagnostic tools

• Specific diagnoses• HSV• Aphthous ulcers• Pemphigus vulgaris

Outline

• An exam finding not a diagnosis

• Ulcer vs. erosion

• Differential diagnosis

• Approach to evaluation• Physical exam• Other diagnostic tools

• Specific diagnoses• HSV• Aphthous ulcers• Pemphigus vulgaris

Ulcer

• An exam finding not a diagnosis

• Many different causes

• Use your exam, labs, studies to narrow down diagnosis

Outline

• An exam finding not a diagnosis

• Ulcer vs. erosion

• Differential diagnosis

• Approach to evaluation• Physical exam• Other diagnostic tools

• Specific diagnoses• HSV• Aphthous ulcers• Pemphigus vulgaris

Ulcer vs. Erosion

• Erosion• Partial to complete loss of epidermis y• Doesn’t penetrate through basement membra e• Red base• Heals without scaring

• Ulcer• Full thickness epidermal loss + penetration through

basement membrane to dermis • Usually yellow-white base• Heals with scarring

https://en.wikipedia.org/wiki/Skin_fissure

Ulcer vs. Erosion

• Important or Nitpicky?

• Important!• Exam findings are different

• Differential https://en.wikipedia.org/wiki/Skin_fissure

Outline

• An exam finding not a diagnosis

• Ulcer vs. erosion

• Differential diagnosis

• Approach to evaluation• Physical exam• Other diagnostic tools

• Specific diagnoses• HSV• Aphthous ulcers• Pemphigus vulgaris

Differential Diagnosis

• Ulcer = morphology

• Differential diagnosis is broad• Infectious

• Inflammatory

• Neoplastic

• ‘Outside Job’

Differential Diagnosis-- Infectious• Viral

• Herpes simplex virus (esp. if immunocompromised host)

• Herpes zoster virus

• Cytomegalovirus

• Bacterial

• Ecthyma (gram positive or gram negative)

• Granuloma inguinale

• Chancroid

• Lymphogranuloma venereum (LGV)

• Treponemal

• Primary syphilis

• Fungal

• Angioinvasive fungi

• Mycobacterial

• Tuberculosis

• Atypical mycobacterial

• Parasitic

• Amebiasis

Differential Diagnosis-- Inflammatory

• Aphthae• Behçet’s disease

• Pyoderma gangrenosum

• Crohn’s disease

• Hailey-Hailey disease (benign familial pemphigus)

• Autoimmune blistering disease• Pemphigus vulgaris• Bullous pemphigoid• Cicatricial pemphigoid• Linear IgA disease• Bullous systemic lupus erythematosus• Epidermolysis bullosa acquisita

Differential Diagnosis-- Inflammatory

• Aphthae• Behçet’s disease

• Pyoderma gangrenosum

• Crohn’s disease

• *Hailey-Hailey disease (benign familial pemphigus)

• *Autoimmune blistering disease Erosion versus ulcer Depth is important• Pemphigus vulgaris• Bullous pemphigoid• Cicatricial pemphigoid• Linear IgA disease• Bullous systemic lupus erythematosus• Epidermolysis bullosa acquisita

Differential Diagnosis-- Neoplastic

• High Grade Squamous Intraepithelial Lesion (HSIL)/ Squamous Cell Carcinoma

• Basal Cell Carcinoma

• Melanoma

• Extramammary Paget’s disease

• Langerhans cell histiocytosis

• Others

Differential Diagnosis– ‘Outside Job’• Drug

• Fixed drug eruption

• Stevens –Johnson syndrome / Toxic epidermal necrolysis (SJS/TEN)• Severe – life threatening

• 2+ mucous membranes involved

• Self-induced

• Diagnosis of exclusion

• Angular ulcers with scarring, dyspigmentation

• Full skin exam

• May have underlying drug use, psychiatric condition

Approach to Evaluation-- Physical Exam• Oral exam (+ ROS)

• Remainder of skin

• Genital exam• Erosion vs. Ulcer

• Shape, distribution of lesions

Approach to Evaluation– Other Diagnostic Tools • Blood Tests

• HIV 1, 2 Ab

• Syphilis screening test• Lab/hospital determines exam

• Syphilis EIA (treponemal test) more common

• Positive indicates history of exposure at some point (may be treated)

• Can have false negatives in primary syphilis

Approach to Evaluation– Other Diagnostic Tools • Blood Tests

• CBC with differential and manual peripheral smear

• HSV Serologies

• Indirect Immunofluorescence

• TB Quantiferon

• Blood cultures

• Folate, B12, zinc, iron

Approach to Evaluation– Other Diagnostic Tools • Swabs

• HSV/VZV

• Multiple tests available

Approach to Evaluation– Other Diagnostic Tools • Others

• Colonoscopy

• CXR

• Referrals

• Collaborate with other specialties

• History

Approach to Evaluation– Other Diagnostic Tools • History

• Ask questions, before and after tests

• Level of sickness (outpatient versus inpatient)

• E.g. May be more likely to biopsy, perform multiple studies in sick patient

Approach to Evaluation– Other Diagnostic Tools • History

• Ask questions, before and after tests

• Drug history

• E.g. Acute onset conjunctival redness, oral and genital sores, dusky skin lesions 5 weeks after starting lamotrigine SJS/TEN

Approach to Evaluation– Other Diagnostic Tools • History

• Ask questions, before and after tests

• Drug history

• E.g. Recurrent painful circular lesions on lips, vulva, skin after taking prn naproxen Fixed Drug Eruption

HSV

• Classic herpetiform (grouped) vesicles on red base• In immunocompetent host

• Deep, expansive, multi-site ulcers• In immunocompromised host

HSV in Immunocompromised Host

• High degree of clinical suspicion• HSV testing (DFA/culture/PCR)• HIV Ab testing• Biopsy for viral tissue culture• Biopsy for H&E, immunostain analysis

• Treatment• First, give treatment dose of anti-virals until fully healed• Then given ongoing suppressive dose• Valacyclovir (better bioavailability), Acyclovir (cheaper)

• If treatment fails, consider CMV co-infection or acyclovir resistance

Aphthae

• Very common

• Oral, Genital

• ~20-60% of people have oral aphthae

• Painful red lesions with yellow-white fibrin base

• Cause unclear• Cell-mediated response to trauma, irritant, virus, bacteria?

Common Acute Presentation• Adolescent girls (~9-18 y.o.)

• Viral prodrome (fever, sore throat, malaise)

• Very painful aphthae

• If severe, may be unable to urinate catheterization required

• Inflammation to viral trigger vs. infection?

• Workup generally focused• HSV swab (DFA/Culture/PCR)• HIV Ab• Syphilis screen

• Treat the inflammation • Severe: Prednisone 1mg/kg PO qam until pain resolves• Mild-mod: Topical clobetesol oint BID to AA

Aphthae Management

• Acute, single episode• Severe: Prednisone 1mg/kg PO qam until pain resolves

• Topical clobetesol oint BID to ulcers

Aphthae Management

• Recurrent• Workup

• HIV Ab

• CBC with diff, peripheral smear (heme/neutropenia)

• B12/folate/zinc/iron levels

• Inflammatory bowel disease

• Behcet’s disease

Aphthae Management

• Recurrent• Treatment

• Colchicine 0.6mg PO BID-TID (SE: diarrhea)

• Dapsone

• Thalidomide

• Pentoxyfylline

• TNF inhibitors (adalimumab, etanercept, infliximab)

A Note on Behçet’s Disease

• Multiorgan, inflammatory disease

• Old Silk Road (Turkish, Middle Eastern, Japan)

• VERY RARE

• 1990 ISG for Behçet’s Disease Criteria• At least 3 episodes oral aphthous ulcers in 1 year• Plus 2 of following

• Recurrent genital aphthae• Uveitis, hypopyion, or retinal vasculitis • Erythema nodosum or acneiform lesions • Positive pathergy test

A Note on Behçet’s Disease• Multiorgan, inflammatory disease

• Old Silk Road (Turkish, Middle Eastern, Japan)

• VERY RARE

• 1990 ISG for Behçet’s Disease Criteria• At least 3 episodes oral aphthous ulcers in 1 year (1) Ask• Plus 2 of following

• Recurrent genital aphthae• Uveitis, hypopyion, or retinal vasculitis (2) Ophtho Exam• Erythema nodosum or acneiform lesions (3) Full Skin Exam• Positive pathergy test

A Note on Behçet’s Disease

• Clinical concerns• Vascular

• Vascular aneurysms fatal

• Thrombophlebitis

• Arthritis

• Cardiac, GI, Renal, Neuro etc.

• Referral to Rheumatology

Autoimmune Blistering Diseases

• Pemphigus vulgaris

• Bullous pemphigoid

• Cicatricial pemphigoid

• Linear IgA disease

• Bullous systemic lupus erythematosus

• Epidermolysis bullosa acquisita

Pemphigus Vulgaris

• Auto-immune blistering disorder• Auto-antibodies to desmoglein 3

• Important to hold the epidermis together in skin and mucosa

• When severe can cause death

• Treatment• Prednisone

• Steroid-sparing immunosuppressants

Pemphigus Vulgaris

• If persistent oral and genital ulcers• Consider this diagnosis• Consider other autoimmune bullous diseases

• Bullous pemphigoid• Cicatricial pemphigoid• Linear IgA disease• Bullous systemic lupus erythematosus• Epidermolysis bullosa acquisita

• Refer to dermatology for evaluation• Biopsy for H&E and Immunofluorescence