Cutaneous Manifestations of Internal Disease

Question 1

What causes NF-1, what chromosome is it on, and how do you remember dis?

Answer 1

Autosomal dominant mutation in tumor suppressor gene neurofibromin, a GTPase in the Ras pathway, on chromosome 17. Remember this because NF-1 is also called von Recklinghausen disease, and there are 17 letters in “von Recklinghausen”.

Question 2

When do neurofibromas first begin appearing in NF-1 and how do they influence develpment? What do they look like?

Answer 2

First start appearing around puberty, there can be thousands of them -> pedunculated flesh-colored papules

Can lead to seizures, learning disabilities, and poor coordination

Question 3

What is the first sign of NF-1?

Answer 3

Cafe-au-lait macules -> flat, light brown, homogenous macules
-> 99% of NF-1 patients have it before age 1

Question 4

What is the most specific clinical finding for NF-1?

Answer 4

Crowe sign -> axillary or inguinal freckling

Question 5

Where and when are plexiform neurofibromas formed? What do they look like?

Answer 5

They occur along peripheral nerves. They are usally formed congenitally.

Create large, tender masses with overlying hyperpigmentation / hypertrichosis. They feel like a bag of worms

Question 6

What are optic gliomas and their complication?

Answer 6

They are a type of pilocytic astrocytoma in adults, and may lead to blindness

Question 7

Why should blood pressure be monitored in patients with NF-1?

Answer 7

Children may develop renal artery stenosis

Adults may develop pheochromocytoma

Question 8

What causes tuberous sclerosis?

Answer 8

Autosomal dominant mutations in tumor suppressors TSC1 and TSC2: hamartin and tuberin.

Question 9

What are common dermatologic lesions seen in tuberous sclerosis?

Answer 9

Ash leaf spots
Angiofibromas
Ungual Fibromas
Shagreen Patches

Question 10

What are Ash leaf spots and angiofibromas? How do you see Ash leaf spots better?

Answer 10

Ash leaf spots - Hypomelanotic macules, accentuated by Wood’s lamp

Angiofibromas - hamartomas of connective tissue / bloood vessels which appear as bumps on face, beginning in childhood and stabilizing by adulthood

Question 11

What are ungual fibromas and Shagreen patches?

Answer 11

Ungual fibromas - tumors of the nailbed

Shagreen patches - Connective tissue hamartomas seen on trunk

Question 12

What brain tumor are you at increased risk for with tuberous sclerosis?

Answer 12

Subependymal giant cell astrocytomas

Question 13

What is factitial dermatitis? How do you tell this is what it is?

Answer 13

Psychiatric condition in which patients self-induce skin wounds and often deny it

Typically the lesions have geometric borders and bizarre distribution, and are easily reachable with your dominant hand

Question 14

What are the three possible skin manifestations of sarcoidosis?

Answer 14

1. Papular sarcoid
2. Plaque sarcoid
3. Lupus pernio

Question 15

What is lupus pernio?

Answer 15

Yellow-red to rust colored papules, plaques, or nodules usually affecting the skin of the nose as well as rest of face.

Question 16

What is erythema nodosum and where does it typically occur?

Answer 16

Painful, erythematous lesions of subcutaneous fat (panniculitis) usually seen on anterior shins.

Question 17

What conditions are associated with erythema nodosum?

Answer 17

Most cases are idiopathic but:

1. Group A Strep - commonly in children
2. Sarcoidosis
3. TB / coccidioido / histo
4. Inflammatory bowel disease
5. Leprosy

Basically, think group A strept + all the conditions which result in granulomatous inflammation

Question 18

What is yellow nail syndrome associated with?

Answer 18

Yellow nails with no cuticles and transverse ridging

-> typically associated with bronchiectasis and pleural effusions

Question 19

What does nail clubbing imply?

Answer 19

Underlying lung disease

Question 20

What are classical signs of venous insufficiency?

Answer 20

Varicosities, edema, ulcers, hemosiderin pigmentation

Stasis dermatitis (mimics cellulitis) and lipodermatosclerosis may develop

Question 21

How should you treat venous insufficiency and stasis dermatitis?

Answer 21

Venous insufficiency - compression stockings -> helps improve pitting edema and venous return

Stasis dermatitis -> Topic corticosteroids and moisturizers

Question 22

What is lipodermatosclerosis and how will the leg appear?

Answer 22

Skin, subcutaneous fat, and deep fascia become progressively hardened (indurated)

-> inverted wine bottle appearance because lower part of leg below calf gets restricted

Question 23

What is pyoderma gangrenosum and what condition is most associated?

Answer 23

Painful ulcer with a “rolled” border
-> initial lesion comes from a pustule or inflamed nodule which ulcerates

-> most associated with inflammatory bowel diseases, especially ulcerative colitis (Crohn’s is mostly associated with erythema nodosum)

Question 24

How should pyoderma gangrenosum be treated?

Answer 24

Let them heal gradually, do not attempt to debride them!

Associated with “pathergy” -> enlargement of lesion with trauma

Question 25

You’ve come across prurigo nodularis before. What condition is it most associated with?

Answer 25

Most common manifestation of renal disease (patients itch due to uremia)

• > pruritic nodules on arms and legs
• > can also be seen in liver disease due to jaundice causing itching

Question 26

What are Lindsay nails also called, what are they, and in what disease are they found?

Answer 26

“Half and half” nails - proximal half of nail appears white, distal half is reddish-brown and does not blanch

Found in end stage renal disease.

Question 27

What skin condition of ESRD is characterized by painful ulcers with a black eschar? What is the most common cause of death in these patients?

Answer 27

Calciphylaxis -> toxicity due to elevated calcium levels secondary to hyperparathyroidism in endstage renal disease

Most common cause of death is staph septicemia due to failure of wound care

Question 28

What scleroderma-like condition does gadolinium contrast for MRI cause if given to patients with ESRD?

Answer 28

Nephrogenic Fibrosing Dermopathy

-> indurated plaques on lower extremities, associatd with yellow plaques. Face is spared.

Question 29

What is acanthosis nigricans and where does it appear?

Answer 29

Epidermal hyperplasia causing elevated, hyperpigmented skin thickening. Appears especially in neck, axilla, and groin

Question 30

What conditions are associated with acanthosis nigricans and how is their onset different?

Answer 30

Insulin resistance - i.e. diabetes, obesity, Cushing syndrome

Visceral malignancy - i.e. gastric adenocarcinoma -> much more rapid onset than insulin-resistance related

Question 31

What ulcerating condition of the shins is associated with diabetes? Must diabetes be present?

Answer 31

Necrobiosis Lipoidica Diabeticorum

Diabetes need not be present, and glucose control will not clear NLD

Question 32

What is granuloma annulare and where does it typically appear? What condition is it associated with?

Answer 32

Grouped papules in an annular configuration, often appearing on the backs of hands as an isolated lesion

Associated with diabetes, resolves spontaneously without treatment

Question 33

What lesions typically appear in diabetes where triglyceride levels excess 3000 to 4000 mg/dL? Where?

Answer 33

Eruptive xanthomas

-> typically on extensor surfaces of extremities, buttocks, and hands

Question 34

What skin changes is Graves’ disease associated with and why?

Answer 34

Pretibial myxedema, due to increased hyaluronic acid in the dermis
-> symmetric, non-pitting yellow-brown waxy papuules and plaques

Question 35

What is polymorphic eruption of pregnancy?

Answer 35

Urticarial papules and plaques that appear within stretch markers during late third trimester
-> very pruritic rash that resolves spontaneously with birth

Question 36

Where does pyogenic granuloma often occur and what condition must be ruled out?

Answer 36

Often occurs on the gums during pregnancy.

Need to rule out amelanotic melanoma

Question 37

What is melasma? What causes it / what does it look like / where is it?

Answer 37

“Mask of pregnancy” - hyperpigmentated poorly demarcated patches, typically on the face. Can also be associated with oral contraceptive use.

Question 38

What is telogen effluvium and when does it happen very commonly? How does it resolve?

Answer 38

Shedding / thinning of hairs as hair follicles enter the shedding (telogen) phase.

Often happens post-partum

Resolves spontaneously, there is no effective treatment, may take up to 18 months

Question 39

Give five major cutaneous manifestations of dermatomyositis.

Answer 39

1. Periungual telangiectasias
2. Gottron’s papules - violaceous papules overlying finger joints
3. Shawl sign - purple erythema of back of neck and posterior shoulders
4. Heliotrope rash - periorbital erythema and edema
5. Mechanics hands - scaly fissures and inflammatory changes of hands bilaterally

Question 40

What malignancies is dermatomyositis associated with?

Answer 40

Ovarian, lung, colorectal, breast, and non-Hodgkin’s lymphoma

Question 41

A patient has flushing episodes which last for about 30 minutes, often associated with dyspnea, abdominal cramping, and diarrhea. What do they most likely have and where is it?

Answer 41

Carcinoid tumor - most common malignancy of the small bowel

Question 42

What skin condition is associated with glucagonoma? Where does it develop and what does it look like?

Answer 42

Necrolytic migratory erythema

Patches of erythema which can become flaccid bullae and desquamate, leaving a collarette of scaling

Tends to favor the flexural areas of groin, buttocks and thighs (intertriginous areas)

Question 43

What condition may glucagonoma be misdiagnosed with? What will patients present with clinically (outside of skin manifestations)?

Answer 43

May be misdiagnosed as intertriginous dermatitis (like diaper rash for adults)

Adults present clinically with new onset diabetes

Question 44

Why are malignancies associated with acanthosis nigrans?

Answer 44

Tumor growth activates insulin-like growth factors, which stimulates EGFRs -> epidermal hyperproliferation

These lesions parallel neoplastic progression and recurrence

Question 45

What is the sign of Leser-Trelat?

Answer 45

Sudden appearance of multiple seborrheic keratoses

-> indicates underlying GI malignancies