Clinical Pearls in Dermatology

Lisa H Scatena, M.D. F.A.A.D.Rocky Mountain Dermatology, Boulder

Assistant Clinical ProfessorDermatology & Internal Medicine

University of Colorado, Denver

6 February 2009

What Can We Glean from the Largest Organ in the Body?

What Can We Glean from the Largest Organ in the Body?

Earlier detection, diagnosis and treatment of systemic diseases.

Where Have We Been and Where Are We Going?

2006- The skin biopsy

2008- Common dermatoses

2009- Systemic diseases and skin findings

2010- ?

Learning Objectives Recognize newly described skin diseases

Review newer skin signs of well-established systemic diseases

Based upon skin findings, make appropriate diagnostic and therapeutic decisions for systemic diseases

Case 1

Case 1: A 54 year old man with diabetes mellitus and chronic renal failure complains of swelling, tightness and darkening of the skin on

his arms and legs. His symptoms have developed over the past 2-3 weeks following a

failed kidney transplant and imaging. Upon further questioning, this patient is most likely to

also complain of:

Case 1: Upon further questioning, this patient is most likely to also complain of:

1. Burning and itching in his arms and legs

2. Changes in his vision3. Colicky abdominal pain4. Difficulty swallowing5. Oral ulcers

Nephrogenic Fibrosing Dermopathy 15 patients with renal disease Extensive thickening and hardening of the skin

with brawny hyperpigmentation Nearly all had extremity lesions, tendency to

spare the trunk Some had diffuse thickening, others papules or

subcutaneous nodules

Cowper et al. Lancet 2000; 356:1000

CD 34

Nephrogenic Fibrosing Dermopathy

Fibrosis may lead to calcification and dermal ossification

Extension from skin and subcutaneous tissue into the underlying fascia and muscle

Flexion contractures continue to worsen with resultant severe disablility

Increased mortality

Nephrogenic Fibrosing Dermopathy

Nephrogenic Fibrosing Dermopathy

The dominant cell is a dual staining CD34-procollagen fibrocyte corresponding to a circulating cell that expresses markers of both connective tissue cells and leukocytes

Aberrant fibrocyte recruitment, activation or proliferation the cause? Possibly related to ischemia

Curr Opin Rheumatol 2003, 15: 785

CD 34

Nephrogenic Fibrosing Dermopathy 33 patients in St Louis with NFD

Most had received dialysis Only 1 patient had not been exposed to gadolinium 4/33 had NOT been exposed to gadolinium for more

than a year (range: 16-68 months)

Gadolinium exposure has some causative role in NFD.

CDC NFD associated with exposure to gadolinium-containing contrast agents-St Louis, Missouri, 2002-2006. MMWR 2007 Feb 23;56;137-41

Nephrogenic Fibrosing Dermopathy Cross sectional study of 186 dialysis patients in

Boston 25/186 had NFD skin changes identified (13%) 94% had exposure to Gadolinium Mortality rate among dialysis patients with NFD was

statistically greater than “usual” dialysis patients

NFD is a predictor of early mortality.

Todd et all. Cutaneous changes of NSF. Predictor of early mortality and associated with gadolinium exposure. Arth Rheum 2007 Sept 28;56:3433.

Nephrogenic Fibrosing Dermopathy

Topical steroids, retinoids, and lactic acid, systemic retinoids, and electron beam all tried without effect

Individual patients have responded to prednisone,plasmapheresis, IVIG, thalidomide, UV-A1, extracoporeal photopheresis and interferon-alpha, many others have not

Improvement of renal function or transplantation may improve NFD, but not always

Current favored therapy is PREVENTION

BJD 2005; 152: 531

PEARL #1Consider alternate imaging processes when possible in patients with renal failure. If a patient must have an MRI, prompt dialysis

after MRI is suggested.

This 63 year old man has been on this medication for years. Not only has he experienced the skin changes below, he has developed arthralgias and a (+) ANCA.

Causative agents for his skin changes include:

1. Amiodarone2. Gold3. Minocycline4. Plaquenil

Minocycline Well known agent to

result in hyperpigmentation as a result of both melanin and iron deposition

Locations Blue-black scars Blue gray legs &

forearms Muddy brown on sun

exposed areas

Reported to cause a lupus-like syndrome

(+) ANA, (+) pANCA Occurs at a greater

rate in those patients on minocycline for longer duration of time

Resolves when minocyline is discontinued

PEARL #2If a positive ROS is elicited for connective tissue disease in minocycline recipients,

consider serologic testing including ANCA.

Case 3: Looking at What We Know from A Different Vantage Point…

Courtesy of Dr. William James

Case 3: A 56 year old woman with arthralgias, malaise, scaling scalp, and intractable itching develops this bizarre eruption. What other findings would you expect on examination?

1. Deep red-violaceous patches on extensor forearms

2. Lichenified, excoriated plaques periumbilical area

3. Scarring alopecia4. Violaceous tender nodules on shins

Arch Dermatol 2000; 136: 665 J Rheum 1999;26:692

DermatomyositisCentripetal Flagellete Erythema

Edematous, erythematous streaks on the trunk and proximal extremities

Histology – interface dermatitis, positive direct immunofluorescence

Parallels disease activity Only reported in dermatomyositis, not seen in

other connective tissue diseases, in a review of 183 patients from one institution

Arch Dermatol 2000; 136: 665J Rheumatol 1999; 26: 692

Dermatomyositis

Dermatomyositis: Gingival Telangiectases

Five patients with juvenile DM 1 boy, 4 girls All had similar nail fold telangiectases Other oral findings of DM include edema,

erosions, ulcers and white plaques

Arch Dermatol 1999; 135: 1370

What finding is most predictive of an underlying malignancy in DM?1. Cutaneous

Necrosis2. Gottron Papules3. Itching4. Mechanics Hands5. Shawl sign

DermatomyositisCutaneous Necrosis

Cutaneous necrosis – rare in adults

1990: 5 cases reported in a study of 32 patients with dermatomyositis In 4 of 5 cases, patients had associated malignancy

7 of 10 in a larger series had malignancy

Positive predictive value of cutaneous necrosis is 71.4%

Cause uncertain, some with antiphospolipid antibodiesArch Dermatol 2003; 139: 539

DermatomyositisRisk of Internal Malignancy

Classic dermatomyositis has a definite association with occult malignancy <25%

Women: ovarian carcinoma Asian men: nasopharyngeal carcinoma

Negative risk factor: Interstitial lung disease

Little-to-no increase risk of malignancy in polymyositis

Lancet 2001; 357:85-86Br J Cancer 2001; 85:41-45

Curr Opin Rheumatol 2000; 12:498-500

DermatomyositisWhat about cutaneous amyopathic DM?

Sontheimer reviewed world literature which reported a total of 300 cases 10% of these were associated with malignancy

Mayo Clinic 1976-1994 found 32/746 patients had cutaneous amyopathic dermatomyositis 25% found to have malignancy in 2-10 year follow-up All were women Lung CA, ovarian CA, breast CA, endometrial CA and

metastatic adenocarcinoma of unknown primary

Dermatol Clin 2002; 20:387-408

DermatomyositisOccult Malignancy Work-up

Repeat malignancy surveillance measures every 6-12 months for the first 3-5 years following the diagnosis

After 5 years, the risk of malignancy returns to that of the general population for that age and sex

Dermatol Clin 2002; 20:387-408

PEARL #3In the case of a new diagnosis of

dermatomyositis in an adult, at a bare minimum, age appropriate screening for

malignancy should be performed. Strongly consider imaging if clinically indicated.

Case 6 month history of this minimally itchy eruption. Started with 1 red patch and spread after application of a prescription medication.

What prescription medication did he put on his skin with this resultant rash?

1. Efudex2. Eucerin Calming

Lotion3. Neosporin ointment4. Retin-A cream5. Triamcinolone cream

Tinea Versicolor Not really a dermatophyte, caused by Malassezia

furfur or pityrosporum ovale As a yeast, considered normal follicular flora As hyphae, results in skin disease Common in summer months Treatment

Azoles,selenium sulfide lotions, Zinc pyrithione soap PO Azoles for difficult to treat cases

Ketoconazole 400mg doses repeated monthly Itraconazole 200mg qd x7days Fluconazole 400mg once monthly

PEARL #4If there is scale, SCRAPE IT!!

64 year old man presents with asymptomatic 1-2mm firm, white-flesh colored bumps all over his face since his 30’s.

5.

PMHx: HTN, history of pneumothorax Medications: Lisinopril, ASA Wears sunscreen routinely 5-10 blistering sunburns in his lifetime

Our patient:

Our patient and his family members are at risk for:1. Adenocarcinoma2. Anticardiolipin

Syndrome3. Basal Cell

Carcinomas4. Factor V Leiden

Deficiency5. Renal Cell

Carcinoma

Birt-Hogg-Dube Syndrome

Multiple smooth skin colored to whitish papules Face 60-70% Neck 80% Upper trunk 90%

Oral fibromas 25% Acrochordons 30% Lipomas and collagenomas 15%

Birt-Hogg-Dube SyndromeAssociated Abnormalities

Skin papules develop in 30’s Pulmonary cysts and pneumothorax, symptoms

begin in late teens or 20s, odds ratio 50.3 Renal cancers, onset in 50s, 10% of hereditary

renal cancer patients with BHD, odds ratio 6.9, abdominal CT and renal ultrasound

Five patients with parotid oncocytomas

JAAD 2000; 43:1120

JAAD 2003; 48:111

Birt-Hogg-Dube Syndrome

Described in 1977 as an autosomal dominant triad of skin findings fibrofolliculomas trichodiscomas acrochordons

Penetrance 88% over age 25, gene isolated on 17p, mutation in gene for protein folliculin

Understanding of cutaneous tumors, relationship to renal cancer and pulmonary cysts recently understood in the past five years

J Am Acad Dermatol 2003;49:698,717

PEARL #5If you see a patient with numerous

monomorphic firm small papules on his face, ASK about family members. If others

in the family have similar bumps, this warrants further evaluation including skin

biopsy and renal imaging.

Associated Disease?

Associated disease?1. Deep fungal infection2. Diabetes Mellitus3. Hepatitis C Virus4. Lupus Erythematosus5. Sarcoidosis

Necrobiosis Lipoidica Diabeticorum

Necrobiosis Lipoidica Diabeticorum Women are over represented 3:1 to men <3% diabetics have NLD

80% DM diagnosis preceeds NLD 10% DM FOLLOWS NLD diagnosis

Chronic indolent course Complicated by ulceration (35%) Increased rate of microvascular disease in

this subset of diabetic patients

PEARL #6If you see a patient with a waxy yellow atrophic plaque on the anterior tibia,

without a diagnosis of diabetes, check for it. If you see a patient with known diabetes

and NLD, aggressive management to minimize the risk of microvascular

complications is a must.

38 yo IVDA, ETOH, HTN with tender plaques that began on his feet and hands.

Which of his pre-existing conditions has likely contributed to his dermatoses?

Alc

ohol

Coca

ine

use

Dia

betes

Mel

litus

Hyp

erte

nsion

IVDA

20% 20% 20%20%20%

10

1. Alcohol2. Cocaine use3. Diabetes Mellitus4. Hypertension5. IVDA

Necrolytic Acral ErythemaHepatitis C

Ten patients, 4 reports 7 women, 3 men Ages 11-55 All hepatitis C positive

Arch Dermatol 2005; 141: 85

Tender well-defined, velvety or scaly surfaced dusky red plaques

Occasional blisters and erosions Usually involves the dorsal feet, but legs

and hands also affected May respond to interferon, ribaviron, or

zinc treatment

Necrolytic Acral ErythemaHepatitis C

PEARL #7A number of cutaneous clues can steer you towards Hepatitis C Virus Infection in the

appropriate patients.

55yo man presents with an indolent onset of thick skin on the back of his neck and shoulders. He also complains of “chipmunk cheeks” which he did not have 6 months ago.

Far and away, the most common association with his finding is:

Am

yloi

dosis

Der

mat

omyo

sitis

Dia

betes

Mel

litus

Hyp

othy

roid

ism

Sys

tem

ic L

upus

Er...

20% 20% 20%20%20%

10

1. Amyloidosis2. Dermatomyositis3. Diabetes Mellitus4. Hypothyroidism5. Systemic Lupus

Erythematosus

Scleredema Characterized by stiffening and hardening of

subcutaneous tissues on face, neck, upper back, and chest

Variants Type 1:

Women primarily Following URI, especially GAS; may involve tongue,

pharnyx (self limiting <2y) Type 2:

No antecedent illness. MUGAS Type 3:

Middle-age men Associated with diabetes mellitus

Scleredema Associated systemic symptoms can include:

Serositis, dysarthria, dysphagia, myositis, parotitis, ocular and cardiac abnormalities

DDx: Scleroderma, scleromyxedema, cellulitis

Treatment: Type 1: self limiting Type 2 and 3: PUVA, cyclophosphamide, corticosteroids

PEARL #8Biopsy THICK skin

Consider fasting glucose, SPEP, UPEP, ASO titer

58 year old man presents with painful genital sores and “thrush” in his mouth.

The thrush has not improved with nystatin swish and spit regimen. He recently got

new glasses, but he still finds his vision has changed and feels as if something is in his

eyes.He wonders if it could be from a lack of Vitamin D because his dermatologist has

beaten into him the need for daily sunscreen.

Direct Immunofluorescence Study

IgG

Your Leading Clinical Diagnosis is:

1. Cicatricial Pemphigoid

2. Herpes Simplex Virus

3. Major Apthous Ulcer Disease/Sutton’s Disease

4. Stevens Johnson Syndrome

5. Vitamin D Deficiency

Anti-Epiligrin Cicatricial Pemphigoid

IgG

Anti-Epiligrin Cicatricial Pemphigoid

Mucosal predominant blistering disease Mouth, eye and genital Skin involvement not uncommon

Pathogenic IgG antibodies against Laminin 5

Arch Dermatol 1994, 130:1521

Cicatricial Pemphigoid

Immunologically distinct immunobullous dieases with scarring

Oral (90%), conjunctival (66%), Cutaneous lesions (25%)

Circulating autoantibodies targeting hemidesmosomal proteins: BP 180, BP 230 and integrins CP with antibodies directed against Laminin 5 or

epiligrin is associated with an increased risk for solid tumors, especially adenocarcinoma.

Vodegel RM, et al JAAD 2003;48:542.

Anti-Laminin 5 Cicatricial Pemphigoid

Retrospective study of 35 patients, median age 65 10 had solitary solid tumors lung, stomach, colon, endometrial

Overall relative risk= 6.8; RR 1y after diagnosis = 15.4

8 of 10 developed cancer AFTER blisters 7 of 8, within 14 months of onset 8 of 8 died within 21 months of diagnosis

Lancet 2001; 357: 1850

PEARL #8Wear your sunscreen. You wouldn’t want an

autoimmune blistering disorder AND a skin cancer.