Ted Rosen, MD Professor of Dermatologyprimarycareupdate2019.com/wp-content/uploads/2019/AP1.pdf · Foot ulcers (neurotrophic) Ac anthosi sigric Bullosis diabeticorum Scleredema M

Ted Rosen, MD

Professor of Dermatology

Baylor College of Medicine

Houston, Texas

Ted Rosen, MD

Professor of Dermatology

Baylor College of Medicine

Houston, Texas

None

The skin is a mirror of the human condition

Window through which we can look inside

Almost every disease expresses itself on the

skin, to a greater or lesser extent

Some manifestations nonspecific, some suggestive

and some closely linked (pathognomonic)

AP1: Cutaneous Signs of Systemic Disease - Ted Rosen, MD

First described 1920 (SBE)

15%-33% BE demonstrate

Fingers >> Toes

M > F

African-American > Caucasian

HOWEVER: very non-specific

Most often trauma; psoriasis, LP; drugs: sunitinib & sorafenib

Int J Dermatol. 2016;55:1304-1310

Manifestation of bacterial sepsis

Pseudomonas, Klebsiella, E. Coli, Serratia, rarely S. Aureus

Solitary, painless, red swelling, may develop bulla, but rapidly forms

painless eschar-covered ulcer

Patient febrile and toxic-appearing

Process only takes 12-24 hours

IMMUNOCOMPROMISED, NEUTROPENIC

IV antibiotics for presumed Pseudomonas

Culture skin, culture blood, look for focus of infectionMed Clin North Am 92:427, 2008

Cutis 90:67, 2012


Meta-analysis of 167 cases in literature 1975-2014

Pseudomonas 73.65%

Other bacteria 17.35%

Fungi 9%

Sick but not immunocompromised (55/167 = 33%)

May be totally healthy (7/167 = 4.2%)

Eur J Clin Microbiol Infect Dis. 2015;34:633-9

Porphyrins in skin due to

excess in blood

Dorsal hands

Photosensitivity (blisters)

Erosions and Milia (heal)

Facial hypertrichosis

Acquired increased porphyrins*

o Alcohol abuse

o HCV

o Iron overload

Genetic enzyme deficiency

Check 24 hour urine porphyrin

o Increased uroporphyrin

Look at urine! Bedside diagnosis

Acquired increased porphyrins*

o Alcohol abuse

o HCV

o Iron overload

Genetic enzyme deficiency

Check 24 hour urine porphyrin

o Increased uroporphyrin

Look at urine! Bedside diagnosis

Me Patient


Caution! Associations:

Hepatitis C infection

Hepatoma

Hemochromatosis

Rx: Phlebotomy (500cc Q2w)

Antimalarial drugs

HCV anti-viral therapyN Engl J Med. 377:862-872, 2017

JAMA Dermatol. 2016;152:1393-1395

Before specific anti-viral therapy After anti-HCV therapy

Necrobiosis lipoidica

Granuloma annulare

Xanthoma

Candida and Tinea

Diabetic dermopathy

Foot ulcers (neurotrophic)

Acanthosis nigricans

Bullosis diabeticorum

Scleredema

Many associations



Granuloma annulare

Xanthoma

Candida and Tinea

Diabetic dermopathy




Scleredema

GroinAxilla

Topical Nystatin, ANY topical azole

Fluconazole 150mg, QOD x 3 doses

Hb A1c = 14.2

Hb A1c = 13.7

Any topical antifungal QD-BID until clear

Terbinafine 250mg QD until clear


Granuloma annulare

Xanthoma

Candida and Tinea

Diabetic dermopathy




Scleredema


Granuloma annulare

Xanthoma

Candida and Tinea

Diabetic dermopathy

Foot /Toe ulcers



Scleredema


3-15% of diabetics develop

Precede 85% LE amputation

Pure neuropathic 45-60%

Pure ischemic 10%

Mixed neuro-ischemic 25-45%

Sensory, Motor, Autonomic

neuropathy all contribute

J Am Acad Dermatol 2014;70:1-18

Medical therapy

Proper footwear, orthotics prn

Correct deformities (claw, hammer)

Debride callus (prevents healing)

Contact casting (off loading)

Revascularization, if indicated (Doppler, Ultrasonography)

D/C smoking

Assess for infection (erythema, swelling): 50% develop

Assess for osteomyelitis (probe to bone: sensitivity 66%

specificity 90%); radiograph has lag; 50% bone gone for

positive radiograph; MRI; Bone biopsy

PDGF, Hydrogel or Dermal dressing, Hyperbaric O2 J Am Acad Dermatol 2014;70:21-44

Prevention: Annual screen

of “at-risk” foot + education

about proper foot care:

2/3-3/4 reduction ulcer

and amputation

J Am Acad Dermatol 2014;70:1-18


Granuloma annulare

Xanthoma

Candida and Tinea

Diabetic dermopathy




Scleredema

Most common, severe or reliable skin signs of diabetes

Rare disease; 3-4th Decade

F>M

Waxy yellow skin

Telangiectasia (coarse)

IF: Ulceration (painful)

11-65% of NLD = diabetic

Given DM, only 0.3% NLD

May appear before DM

Control DM (may not help)

Steroids: systemic, topical, IL

Pentoxyfylline 400mg TID

“Drug looking for a disease”

Surgery w/ grafting

Phototherapy: PUVA, PDT

No consensus; Nothing greatInt J Dermatol. 2017;56:1319-1327

J Dtsch Dermatol Ges. 2017;15:151-157


Ulcerative is painful

Emergency

Surgical excision/grafting

Biphasic: children/adults

F>M

Extremities: hands, feet, ankles, forearms

Annular (round), red plaques

Small papules in ring

Itchy often

12% DM; rare cancer, viral

Steroids: topical or IL

“Scarification” (trauma)

TNF-alfa inhibition

Various clinical forms

May be associated w/

dyslipidemia

May not be associated

w/ dyslipidemia

Eruptive

Tendinous

Tuberous

Xanthelasma


TYPE CLINICAL FEATURES TYPE DYSLIPIDEMIA

Xanthelasma Canthi, Upper lid, Yellow + Lipid abnormality

Hypercholersterolemia

Eruptive Yellow grouped papules

Buttocks, Elbows, Knees

High TG/Diabetes

Types I, II, IV

Plane Flat yellow patches

Palm, Neck, Chest

Primary Biliary Cirrhosis

Type III; Myeloma w/o HL

Tuberous Nodules: Elbows, Knees High TG/Diabetes

Type II, III

Tendinous Nodules: Elbows, Knees

and Achilles tendon;

Hands and Feet

Almost exclusively in

Type II

TYPE CLINICAL FEATURES TYPE DYSLIPIDEMIA

Xanthelasma Canthi, Upper lid, Yellow + Lipid abnormality

Hypercholersterolemia

Eruptive Yellow grouped papules

Buttocks, Elbows, Knees

High TG/Diabetes

Types I, II, IV

Plane Flat yellow patches

Palm, Neck, Chest

Primary Biliary Cirrhosis

Type III; Myeloma w/o HL

Tuberous Nodules: Elbows, Knees High TG/Diabetes

Type II, III

Tendinous Nodules: Elbows, Knees

and Achilles tendon;

Hands and Feet

Almost exclusively in

Type II

Monoclonal gammopathy

Multiple myelomaActa Derm Venereol. 2015;95:762-3

Alopecia Pruritus Vitiligo Xerosis Onycholysis

Hyperthyroid

Hypothyroid



Hyperthyroid √ √ √

Hypothyroid √ √ √ √







Any age

F>M

Firm nodules, plaques

Pre-tibial leg

Accumulation mucin

Thyroid dysfunction:

Grave’s, Hashimoto’s


ACTH Dependent

Cushing’s Disease

Ectopic ACTH (tumors)

Ectopic CRF (tumors)

ACTH Independent

Adrenal adenoma, CA

Primary adrenal hyperplasia

McCune-Albright Syn

Exogenous steroids

ACTH Dependent

Cushing’s Disease

Ectopic ACTH (tumors)

Ectopic CRF (tumors)

ACTH Independent

Adrenal adenoma, CA

Primary adrenal hyperplasia

McCune-Albright Syn

Exogenous steroids

Acne

Moon facies

Tinea

Striae

Skin atrophy

“Buffalo Hump”

Central obesity

Acne

Moon facies

Tinea

Striae

Skin atrophy

“Buffalo Hump”

Central Obesity


Central obesity

Striae

Acne

Moon facies

Tinea

Striae

Skin atrophy

“Buffalo Hump”

Central obesity

Always think of the

metabolic syndrome

with psoriasis!

Roughly 30-40% of

plaque psoriasis pts

Metabolic Syndrome;

Espec >60

Arch Dermatol 147:419, 2011

19 yo


Arch Dermatol Res 298: 321, 2006; Br J Dermatol 157:68, 2007; J Am Acad Dermatol 57:347, 2007

Condition OR 95% CI

Metabolic

Syndrome5.92 2.78 – 12.8

DM Type II 2.48 1.70 – 3.61

Hypertension 3.27 2.41 – 4.43

Dyslipidemia 2.09 1.23 – 3.54

Coronary artery disease 1.77 1.07 – 2.93

COPD 1.63 1.47 - 1.83

Alcohol (heavy) 3.61 1.85 – 7.07

Tobacco 2.96 2.27 – 3.84

Metabolic Syndrome

Obesity alone

Hypertension

MI, CVA

Infl Bowel Disease

Lymphoma

Osteoporosis

ADD, DepressionAm J Clin Dermatol. 2018 Aug 30. doi: 10.1007/s40257-018-0383-4.

Adequate moisturization

Avoid triggers

Topical steroids

TCI (tacrolimus)

Topical PDE4 blocker

(Crisaborole)

Systemic IL4/IL13

Monoclonal antibodyAm J Clin Dermatol. 2018 Aug 30. doi: 10.1007/s40257-018-0383-4.

• IL-4 and IL-13 are type 2/Th2 cytokines

that are thought to mediate many features

of AD

• Dupilumab is a fully human

monoclonal antibody directed against

the IL-4Rα subunit common to both

the IL-4 and IL-13 receptors

Type I receptor: IL-4

B cells, T cells, monocytes, eosinophils, fibroblasts

Type II receptor: IL-13

Epithelial cells, smooth muscle cells, fibroblasts,

monocytes, activated B cells

IL-4 IL-13

IL-4Rα IL-4Rα


“Itch Cytokine”

Malnutrition, Vegan diet

Blood loss (periods, GI)

Malabsorption

Helicobacter infection

Gastritis

Drugs: PPI, ASA

Bleeding disorders

o eg. von Willebrand’s dis

Pregnancy

ESKD (erythropoietin)

CHF*

Intravascular hemolysis

Pallor: Creases, Conjunctiva Koilonychia (Spoon nails)


Increase dietary iron (red meat)

o Avoid calcium, tannins (tea, coffee, red wine)

Oral iron supplementation

o Ferrous fumarate, sulfate, gluconate

o Continued 3mo past normalization (replete stores)

Intravenous iron supplementation

o Polymaltose, carboxymaltose, dextran, gluconate

J Crohns Colitis 2018;12:197-203.

1/3 skin lesion precedes IBD

Younger patients

80-90% respond TNF-α blockers

Seen with advanced renal disease (ESKD)

Rare: 5% of ESKD

F>M, W>B, Obesity, DM

High mortality: 60-80% die within 6 months

o Sepsis

Calcification in arterial vessels: necrosis of skin


Purpuric patches that eventuate into eschar

EXTREME pain

“Fatty areas”

Debridement of dead tissue; Diet (↓Ca, P)

Cinacalcet (PO)

Sodium thiosulfate (IV)

Half and Half Nails Terry’s Nail

Body turns red

Widespread scaling

Itchy

Risks: infection/sepsis

high output CHF

THINK CANCER

Review: Actas Dermatosifiliogr 2018;Oct 10 epub


Pre-existing skin

disease (eg Psoriasis)50%

Drug reaction 10%

Malignancy

(may be occult)10%

Idiopathic 30%

Dermatol Clin 18:405, 2000

After 4th decade

M>F

Red, scaly, patch/plaque

Any body location

Minimally Sx

GI, GU, Respiratory internal cancer due to….

Arsenic exposure

Curettage & Desiccation

Surgical excision

Radiation

Topical therapy (off label)

o 5% 5-FU

o 5% Imiquimod

o .05% Ingenol mebutateCLL discovered

Either severe insect bite reactions (typically to mosquito bites) or an insect bite-like reaction associated with….

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Am J Dermatopathol 27:290-95, 2005


Multisystem disease

Skin, Joints, Organs

Malar rash

Bright red plaques

Can have discoid lesions

ACR/EULAR Criteria

Localized Morphea

No systemic involvement

CREST

Systemic sclerosis

o Esophagus

o Joint mobility

o Heart and Lungs

Localized Morphea


CREST

Systemic sclerosis

o Esophagus

o Joint mobility

o Heart and Lungs


Localized Morphea


CREST

Systemic sclerosis

o Skin tight; loss pigment

o Esophagus

o Joint mobility

o Heart and Lungs

Localized Morphea


CREST

Systemic sclerosis

o Skin tight; loss pigment

o Esophagus

o Joint mobility

o Heart and Lungs


Proximal muscle weakness (getting out of chair, walk stairs)

Elevated muscle enzymes (eg CPK, aldolase)

Abnormal EMG; inflammation on muscle biopsy

Autoantibodies: Anti-TIF1γ, NXP2, SAE, MDA5, Jo-1, Mi2, PL-7, PL-12, MJ

Anti-TIF1γ & NXP-2 especially associated w/ malignancy

Anti-TIF1γ + (50-75% cancer) and NXP-2+ (13.6% cancer)

Crowe’s Sign

Axillary freckling

30% NF-1

Fever 96%

Lymphadenopathy 74%

Pharyngitis 70%

Rash 33-70%

Myalgia/Arthraligia 54%

Diarrhea 32%

Headaches 32%

Nausea/Vomiting 27%

Hepatomegaly 14%

Weight Loss 13%

Neurologic symptoms 12%


Acute Retroviral Syndrome

NON-SPECIFIC

Severe zoster: ~2% HIV+

May be first sign of HIV+

5 doses over 3 wks

Ivermectin 200ug/kg


Multiple Associations

Inflammatory

panniculitis

F:M = 6:1

Ages 20-45 (Peak 30)

Resolve with bruise

Hypersensitivity to….

Dermatol Online J. 2014;20(4):22376

Deep, hot, painful erythematous nodules

Legs and knees

2-50 lesions (avg 6-12)

Resolve with bruise

Fever, Malaise, Arthralgia (knees most)

Dermatol Online J. 2014;20(4):22376

Treatment:

Stop drugs; Treat infections

Treat underlying conditions (IBD)

Bedrest

Compression

Anti-inflammatory drugs

SSKI (hard to get)

Oral tetracyclines

Potent topical, IL, or systemic corticosteroids

ASSOCIATIONS:

Sarcoidosis (Lofgren Syndrome)o Along with hilar adenopathy

Active TB, Pharyngitis (Strep)

IBD: Crohn’s and UC

Drugs: Sulfa, NSAIDS incl ASA

Pregnancy or OCP’s

“Idiopathic”

Clin Gastroenterol Hepatol. 2017;15(1):25-36.e27.

Massive hair loss

>100 normal QD hair loss

All hairs shed: “telogen” or resting “club hairs”

Starts 2-3 months AFTER inciting event; Continues 2-3 mo; stabilizes 6mo; regrowth over 3 mo

CLUB HAIR


Post-partum

Febrile illness

Post-operative

Psychic stress

Major weight loss

D/C OCP

Jetlag

Drug-induced

Cimetidine/Ranitidine

Coumarins/Heparin

Atenolol/Metoprolol

Levodopa/Lithium

Naproxen/Sulindac

Isotretinoin/Acitretin

Stop inciting factor(s)

Tincture of time may suffice (benign neglect)

With no obvious reason…..

Drugs: Curr Drug Saf 1:301, 2006

Eating disorders: Am J Clin Dermatol 6:165, 2005

Stress/Surgery: J Am Acad Dermatol 52(2Suppl1):S12-16, 2005

Clin Exp Dermatol 27:389, 2002

Exp Dermatol 8:305, 1999

Telogen Effluvium

Enlarging painful ulcer

Severe, unremitting 64%

Edge may be purple

Edge may be undermined

Legs common site (78%)

Peri-stomal variant

Pathergy! +ANCA (not diagnostic)

Neutrophillic Dermatosis of Dorsal HandPeristomal Pyoderma Gangrenosum

IBD: both UC and Crohn’s

Rheumatoid arthritis

Myeloid dyscrasia

Then, rarely…..

Hepatitis

PAPA Syndrome

Granulomatous vasculitis

Levamisole-cut cocaine

Drugs: Isotretinoin

Propylthiouracil

Sunitinib

About 50% have no

obvious underlying

factor


AVOID SURGERY OR DEBRIDEMENT

Oral immunosuppresives: prednisone, cyclosporine

o IV steroid pulse

Second line: MTX, cyclophosphamide, mycophenolate mofetil

Biologic drugs (off-label), particularly TNF-alfa blockers

Others; Dapsone, IVIg, thalidomide

Smaller lesions: topical or IL steroids, tacrolimus ointment,

oral doxycycline or minocycline, SSKI

Outlook: UNPREDICTABLE

“Surgical interventions, including aggressive ulcer

excision, recipient site preparation and autologous

skin grafting, have to be avoided during the active

phase of the disease due to the likely occurrence

of new lesions at surgical sites and the potential

worsening of the original lesions.”

Hautarzt 2010;61:345 Am Surg 2011;77:1644

82 year-old female

Trips and falls to floor at home

Two days later, presents to

derm to “get rid of bruise and

bump”

PMH: On Plavix for Afib and

Victoza for T2DM

ROS: headache (VAS 8), nausea

A. Advise ice application

B. Advise heat application

C. Drain forehead

hematoma

D. CT scan of brain

E. Apply Arnica cream

CT scan

Subdural hematoma

CLASSIC case (older, anticoag)

Neurosurgery that afternoon

Saved a life!


Documents

Ted Rosen, MD Professor of Dermatologyprimarycareupdate2019.com/wp-content/uploads/2019/AP1.pdf · Foot ulcers (neurotrophic) Ac anthosi sigric Bullosis diabeticorum Scleredema M