Clinical Pearls in Dermatology
Lisa H Scatena, M.D. F.A.A.D.
Rocky Mountain Dermatology, Boulder
Assistant Clinical Professor
Dermatology & 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 vision
3. Colicky abdominal pain
4. Difficulty swallowing
5. 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 #1
Consider 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. Amiodarone
2. Gold
3. Minocycline
4. Plaquenil
Minocycline
Well known agent to Reported to cause a
result in lupus-like syndrome
hyperpigmentation as
a result of both (+) ANA, (+) pANCA
melanin and iron Occurs at a greater
deposition rate in those patients
Locations on minocycline for
Blue-black scars
longer duration of
Blue gray legs &
time
forearms Resolves when
Muddy brown on sun minocyline is
exposed areas discontinued
PEARL #2
If 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 alopecia
4. Violaceous tender nodules on shins
Dermatomyositis
Centripetal 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: 665
J Rheumatol 1999; 26: 692
Arch Dermatol 2000; 136: 665
J Rheum 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
Necrosis
2. Gottron Papules
3. Itching
4. Mechanics Hands
5. Shawl sign
Dermatomyositis
Cutaneous 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 antibodies
Arch Dermatol 2003; 139: 539
Dermatomyositis
Risk 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; 357:85-86
Br J Cancer 2001; 85:41-45
Curr Opin Rheumatol 2000; 12:498-500
Dermatomyositis
What 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
Dermatomyositis
Occult 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 #3
In 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. Efudex
2. Eucerin Calming
Lotion
3. Neosporin ointment
4. Retin-A cream
5. 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 #4
If 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. Adenocarcinoma
2. Anticardiolipin
Syndrome
3. Basal Cell
Carcinomas
4. Factor V Leiden
Deficiency
5. 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 Syndrome
Associated 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 #5
If 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 infection
2. Diabetes Mellitus
3. Hepatitis C Virus
4. Lupus Erythematosus
5. 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 #6
If 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?
1. Alcohol 20% 20% 20% 20% 20%
2. Cocaine use
3. Diabetes Mellitus
4. Hypertension
5. IVDA
us
l
DA
e
on
ho
us
lit
si
IV
o
el
ne
lc
n
te
M
A
ai
er
es
oc
yp
et
C
H
b 10
ia
D
Necrolytic Acral Erythema
Hepatitis C
Ten patients, 4 reports
7 women, 3 men
Ages 11-55
All hepatitis C positive
Arch Dermatol 2005; 141: 85
Necrolytic Acral Erythema
Hepatitis C
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
PEARL #7
A 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:
1. Amyloidosis 20% 20% 20% 20% 20%
2. Dermatomyositis
3. Diabetes Mellitus
4. Hypothyroidism
5. Systemic Lupus
Erythematosus
s
us
s
m
i
iti
...
os
is
lit
s
Er
d
d
el
yo
oi
oi
s
M
om
r
pu
yl
hy
es
m
Lu
at
ot
et
A
m
yp
b
ic
er
ia
em
H
D
D
st
10
Sy
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 #8
Biopsy 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 #8
Wear your sunscreen. You wouldn’t want an
autoimmune blistering disorder AND a
skin cancer.