Skin and systemic disease

Question 1

What is Curth’s postulate?

Answer 1

Curth’s postulates are criteria used to identify a consistent relationship between an internal malignancy and a cutaneous disorder:

• concurrent onset
• parallel course
• uniform site or type of neoplasm
• statistically significant association
• genetic linkage

Question 2

What dermatological conditions are often seen in cancer patients?

Answer 2

• Carcinoid Syndrome
• Paraneoplastic pemphigus
• Erythema Gyratum Repens
• Acquired hypertrichosis
• Leser Trelat
• Bazex Syndrome
• Ectopic ACTH syndrome
• Pagets Disease: normal and extra-mammary

Question 3

Describe carcinoid syndrome and how it presents dermatologically

Answer 3

Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and less frequently, heart failure, emesis and bronchoconstriction. It is caused by endogenous secretion of mainly serotonin and kallikrein.
Signs include:
– Episodic flushing, mins –hours, no trigger
– Facial telangiectasia (spider veins)
– Usually caused by GI carcinoid, often with liver mets
– If from bronchial or ovarian tumour, no liver mets

Question 4

Describe paraneoplastic pemphigus and how it presents dermatologically

Answer 4

Paraneoplastic pemphigus (=blistering skin condition) is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes.
o Erosive stomatitis (ulcers/erosions of oral mucosa and lips)
o Rash
o Non-hodgkins, Castlemans disease (produces the autoantibody)

Question 5

Describe Erythema gyratum repens and how it presents dermatologically

Answer 5

Erythema gyratum repens (also known as “Gammel’s disease”) is a figurate erythema that is rapidly moving and usually a marker of underlying cancer, usually from the lung. Very rarely seen
o Concentric erythematous lesions
o Variable sites & types of malignancy

Question 6

What is the other name for Gammels disease?

Answer 6

Erythema gyratum repens

Question 7

Describe acquired hypertrichosis lanuginosa, what conditions its linked to and how it presents dermatological

Answer 7

Acquired hypertrichosis lanugo-type or hypertrichosis lanuginosa acquisita (HLA) is often associated with metabolic and endocrine disorders and use of certain drugs. Colloquially known as “Werewolf syndrome”

• Acute onset of lanugo hairs at face and body
• Lanugo hairs are the ones found on newborns, rare in adults
• Colorectal ca > lung > breast, usually advanced
• Also often seen in those with eating disorders

Question 8

Describe Leser-Trélat, what conditions its linked to and how it presents dermatological

Answer 8

The Leser-Trélat sign is the explosive onset of multiple seborrheic keratoses (many pigmented skin lesions), often with an inflammatory base. This can be an ominous sign of internal malignancy as part of a paraneoplastic syndrome. In addition to the development of new lesions, preexisting ones frequently increase in size and become symptomatic

Question 9

Describe Bazex syndrome, what conditions its linked to and how it presents dermatological

Answer 9

o Hyperkeratosis of extremities e.g. hands, feet, ears, nose
o Resembles psoriasis, non-specific fx on skin biopsy
o Gastric, colon, biliary adenocarcinomas, bronchial, oropharyngeal

Question 10

Describe ectopic ACTH syndrome, and how it presents dermatologically

Answer 10

• Tumour production of ACTH leads to generalised hyperpigmentation
• ACTH -> Inc. MSH -> release of melanin from melanocytes
• Tanned skin and hyperpigmention of buccal mucosa

Question 11

Describe classic Paget’s and extra-mammary Paget’s, and how it presents dermatologically

Answer 11

Pagets Disease:
– Eczematous plaque at nipple/areola
– Affects 1-4% of women with breast cancer
– Extension of underlying ductal adenocarcinoma

Extra-mammary Pagets:
– Often a primary intraepithelial adenocarcinoma
– Occasionally secondary to underlying visceral tumour: bladder, colon (why its seen near the anus and genitalia)

Question 12

What are 2 conditions strongly associated with cancer?

Answer 12

• Acanthosis Nigricans

* Dermatomyositis

Question 13

Describe Acanthosis Nigricans, and how it presents dermatologically

Answer 13

Acanthosis nigricans is a skin condition characterized by areas of dark, velvety discoloration in body folds and creases. The affected skin can become thickened. Most often, acanthosis nigricans affects your armpits, groin and neck.

Linked to cancer and diabetes

Question 14

What skin conditions presents as a dark velvety appearance of skin in body folds and creases?

Answer 14

Acanthosis nigricans

Question 15

When should you be concerned about Acanthosis nigricans?

Answer 15

Can preceed malignancy (gastric adenocarcinoma). ?related to by-products. Concern if:
o	Older patient, rapid onset
o	Other skin signs
o	Involves lips
o	Weight loss

Question 16

Describe Dermatomyositis, and how it presents dermatologically

Answer 16

Inflammatory myopathy + rash
– Periorbital heliotrope rash
– Gottrons papules: red maculo-papular lesions over bony prominences e.g. over knuckles
– Shawl sign – seen on chest and across the back
– Photosensitive poikiloderma
– Scalp erythema

Question 17

What are Gottrons papules?

Answer 17

Gottrons papules: red maculo-papular lesions over bony prominences e.g. over knuckles

Seen in Dermatomyositis

Question 18

What condition presents dermatologically with periorbital heliotrope rash, gottrons papules, shawl sign rash, photosensitive poikiloderma and scalp erythema, as well as symptoms of weak/painful muscles?

Answer 18

Dermatomyositis

Question 19

Describe bullous pemphigoid, what conditions its linked to and how it presents dermatologically

Answer 19

AI condition causing annular blister rash

May be associated with cancer

Question 20

Describe Sweets syndrome, what conditions its linked to and how it presents dermatologically

Answer 20

acute febrile neutrophilic dermatosis, characterized by the sudden onset of fever, an elevated WBC, and tender, red, well-demarcated papules and plaques that show dense infiltrates by neutrophil granulocytes on histologic examination, often after infections

Linked to cancer

Question 21

Describe pyoderma gangrenosum, what conditions its linked to and how it presents dermatologically

Answer 21

Pyoderma gangrenosum - condition that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs (shins). When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers.

Linked to IBD and some malignancies

Question 22

Describe acquired ichthyosis, what conditions its linked to and how it presents dermatologically

Answer 22

Acquired ichthyosis - non-hereditary condition, dry and rough skin with scaling (“fish scale” skin), not inherited, linked to deficiencies/tumour

Linked to cancer

Question 23

Describe acquired angioedema, what conditions its linked to and how it presents dermatologically

Answer 23

Acquired angioedema – AI/idiopathic disease causing swelling of face and lips not caused by allergy. Can be linked to tumours

Linked to cancer

Question 24

Describe primary systemic amyloidosis, what conditions its linked to and how it presents dermatologically

Answer 24

Primary systemic amyloidosis – build up of amyloid deposits

Linked to cancer

Question 25

What are some genetic tumour syndromes which can present dermatologically?

Answer 25

Peutz-Jeghers: melanosis, colon hamartomas Muir-Torre: sebaceous tumours, keratoacanthomas, GI, breast, GU Neurofibromatosis: Café au lait, Ax freckles, Neurofibromas, nerve sheath, phaeoCCyT, carcinoid MEN syndromes: angiofibromas, neuromas, lichen or macular amyloid (MEN2), endocrine, P’s Xeroderma pigmentosum: inability to repair sun damage, sarcoma, leukaemia, GI, lung Howel-Evans: palmoplantar keratoderma, oesophageal

Question 26

What is Peutz-Jeghers syndrome?

Answer 26

Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of: o Benign hamartomatous polyps in the gastrointestinal tract - big lumps on GI mucosa o Hyperpigmented macules on the lips and oral mucosa (melanosis) - small brown spots on lips and mouth

Question 27

What genetic cancer syndrome can be recognised by benign polyps on the GI mucosa and hyperpigmented macule on the lips and oral mucosa?

Answer 27

Peutz–Jeghers syndrome

Question 28

How is Peutz–Jeghers syndrome inherited?

Answer 28

Autosomal dominant

Question 29

Describe Muir-torre syndrome

Answer 29

Muir–Torre syndrome (MTS) is a rare hereditary, autosomal dominant cancer syndrome that is thought to be a subtype of HNPCC. Individuals are prone to develop cancers of the colon, genitourinary tract, and skin lesions, such as: o Keratoacanthomas - common low-grade skin tumour that is believed to originate from the neck of the hair follicle o Sebaceous tumors – malignant tumour that arises from sebaceous glands

Question 30

What genetic cancer syndrome can be recognised by keratocanthomas (tumours arising from hair follicles) and sebaceous tumours?

Answer 30

Muir–Torre syndrome (MTS)

Question 31

What genetic cancer syndrome causes patients to be prone to develop cancers of the colon, genitourinary tract, and skin lesions?

Answer 31

Muir–Torre syndrome (MTS)

Question 32

How is Muir–Torre syndrome (MTS) inherited?

Answer 32

Autosomal dominant

Question 33

Describe neurofibromatosis

Answer 33

Neurofibromatosis (NF) is a group of three conditions in which tumors grow in the nervous system. The three types are: o Neurofibromatosis type 1 (NF1) – light brown spots on skin, freckles on armpits and groin, small bumps within nerves and scoliosis. Tumours generally non cancerous o Neurofibromatosis type 2 (NF2) – hearing loss, early onset cataracts, balance problems, flesh coloured skin flaps, muscle wasting. Tumours generally non-cancerous o Schwannomatosis - multiple cutaneous schwannomas, central nervous system tumors, and other neurological complications, excluding hallmark signs of NF.

Question 34

Describe multiple endocrine neoplasia (MEN) syndrome

Answer 34

The term multiple endocrine neoplasia (MEN) encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign. Benign or malignant tumors of nonendocrine tissues occur as components of some of these tumor syndromes. MEN syndromes are inherited as autosomal dominant disorders

Question 35

How is multiple endocrine neoplasia (MEN) syndrome inherited?

Answer 35

Autosomal dominant

Question 36

Describe Xeroderma pigmentosum

Answer 36

Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient. Blotchy sun damaged appearing skin – very close care of skin in the sun

Question 37

What genetic cancer syndrome results in an ability to repair damage of the skin from sun?

Answer 37

Xeroderma pigmentosum

Question 38

How is Xeroderma pigmentosum inherited?

Answer 38

Autosomal recessive

Question 39

Describe Howel-Evans syndrome

Answer 39

Howel–Evans syndrome is an extremely rare condition involving the thickening of the skin in the palms of the hands and the soles of the feet (hyperkeratosis). This familial disease is associated with a high lifetime risk of esophageal cancer.

Question 40

What tumour syndrome is associated with an increased risk of oesophageal cancer?

Answer 40

Howel-Evans syndrome

Question 41

What cancer is closely associated with Howel-Evans syndrome?

Answer 41

Oesophageal cancer

Question 42

What genetic tumour syndrome presents with hyperkeratosis (thickening of skin on palms and soles)?

Answer 42

Howel-Evans syndrome

Question 43

Describe some dermatological conditions associated with genetic GI disease?

Answer 43

Hereditary haemorrhagic telangiectasia – rare AD genetic disorder leading to abnormal blood vessel formation in the skin, mucus membranes and various organs (lung, liver, brain) Ehlers danlos (collagen) – genetic connective tissue disorder. Causes loose joints, stretchy skin and abnormal scar formation Pseudo xanthoma elasticum (elastic) - genetic disease that causes fragmentation and mineralization of elastic fibers in some tissues. The most common problems arise in the skin and eyes, and later in blood vessels in the form of premature atherosclerosis. Blue rubber bleb naevus syndrome - rare condition that is characterized by numerous malformations of the venous system that significantly involve the skin and visceral organs; appear as blue blebs All can cause GI haemorrhage

Question 44

Describe Hereditary haemorrhagic telangiectasia

Answer 44

Hereditary haemorrhagic telangiectasia – rare AD genetic disorder leading to abnormal blood vessel formation in the skin, mucus membranes and various organs (lung, liver, brain). Can cause GI haemorrhage

Question 45

Describe Ehlers danlos

Answer 45

Ehlers danlos (collagen) – genetic connective tissue disorder. Causes loose joints, stretchy skin and abnormal scar formation. Can cause GI haemorrhage

Question 46

Describe pseudoxanthoma elasticum

Answer 46

Pseudo xanthoma elasticum (elastic) - genetic disease that causes fragmentation and mineralization of elastic fibers in some tissues. The most common problems arise in the skin and eyes, and later in blood vessels in the form of premature atherosclerosis. Can cause GI haemorrhage

Question 47

Describe blue rubber bleb naevus syndrome

Answer 47

Blue rubber bleb naevus syndrome - rare condition that is characterized by numerous malformations of the venous system that significantly involve the skin and visceral organs; appear as blue blebs. Can cause GI haemorrhage

Question 48

Describe malignant atrophic papulosis (degos disease)

Answer 48

Malignant atrophic papulosis (degos disease) - form of occlusive small vessel vasculopathy. The blood vessels affected include those supplying the skin, gastrointestinal tract and central nervous system. – Linked to reccurent GI haemorrhage

Question 49

What vitamin deficiencies present dermatologically?

Answer 49

Vitamin A Vitamin C Niacin

Question 50

How does vitamin A deficiency present dermatologically?

Answer 50

Vitamin C deficiency – scurvy (first manifested as rough dry skin and corkscrew hair growth). Also known to cause hyperkeratosis pillaris (bumpy rough skin, especially present on upper arms)

Question 51

How does niacin deficiency present dermatologically?

Answer 51

Niacin deficiency - causes “Casal’s necklace” pigmented rash around neck, sign of pylagera (diarrhea, dermatitis, dementia, death)

Question 52

List some skin signs of diabetes

Answer 52

* Acanthosis nigricans * Acral erythema - red peeling palms and soles * Carotenemia – orange discolouration * Diabetic bullae – blisters * Diabetic dermopathy – “shin spots”, dull-red papules that progress to well-circumscribed, small, round, atrophic hyperpigmented skin lesions usually on the shins. * Disseminated granuloma annulare - widespread skin- coloured, pinkish or slightly mauve-coloured patches * Eruptive xanthomas - crops of small, red-yellow papules; Most commonly arise over the buttocks, shoulders, arms and legs but may occur all over the body * Necrobiosis lipoidica - necrotising skin condition that usually occurs in patients with diabetes mellitus but can also be associated with rheumatoid arthritis; shiny red -brown or yellowish patches * Rubeosis - neovascularization of the iris * Scleredema - rare, self-limiting skin condition defined by progressive thickening and hardening of the skin, usually on the areas of the upper back, neck, shoulders and face. Appears dark

Question 53

Describe aural erythema

Answer 53

Acral erythema – red peeling palms and soles of feet Seen in diabetes

Question 54

Describe diabetic dermopathy

Answer 54

Diabetic dermopathy – “shin spots”, dull-red papules that progress to well-circumscribed, small, round, atrophic hyperpigmented skin lesions usually on the shins. Seen in diabetes

Question 55

Describe disseminated granuloma annulare

Answer 55

Disseminated granuloma annulare - widespread skin- coloured, pinkish or slightly mauve-coloured patches Seen in diabetes

Question 56

Describe eruptive xanthoma

Answer 56

Eruptive xanthomas - crops of small, red-yellow papules; Most commonly arise over the buttocks, shoulders, arms and legs but may occur all over the body Seen in diabetes

Question 57

Describe necrobiosis lipoidica

Answer 57

Necrobiosis lipoidica - necrotising skin condition that usually occurs in patients with diabetes mellitus but can also be associated with rheumatoid arthritis; shiny red -brown or yellowish patches Seen in diabetes

Question 58

Describe scleroderma

Answer 58

Scleredema - rare, self-limiting skin condition defined by progressive thickening and hardening of the skin, usually on the areas of the upper back, neck, shoulders and face. Appears dark

Question 59

How can hyperthyroidism present dermatologically?

Answer 59

Hyperthyroid – proctosis, markings on leg, pretibial myxoedema

Question 60

How can hypothyroidism present dermatologically?

Answer 60

Hypothyroid – “peaches and cream” face, look tired

Question 61

Describe the signs of cutaneous lupus

Answer 61

Presents as annular markings on body and “butterfly marking” on face (redness on cheeks and nose)

Question 62

List some skin conditions caused by autoimmune reactions

Answer 62

* Cutaneous lupus * Cutaneous vasculitis * Alopecia * Vitiligo

Question 63

Describe alopecia areata

Answer 63

Alopecia areata – follicles are “asleep” so can start working at any time again though may take some time

Question 64

What type of alopecia is sometimes reversible i.e. hair can grow back?

Answer 64

Alopecia areata

Question 65

What type of alopecia is irreversible i.e. hair does not grow back?

Answer 65

o Scarring alopecia | o Androgenic alopecia (male-pattern hair loss

Question 66

What is vitiligo?

Answer 66

Vitiligo is a disease in which the pigment cells of the skin, melanocytes, are destroyed in certain areas. Symptoms and signs of vitiligo include loss of skin color in the form of depigmented, or white, patches of skin in any location on the body.

Question 67

What is linked to episodic flushing and facial telangiectasia (spider veins)?

Answer 67

Carcinoid syndrome

Question 68

What conditions is linked to erosive stomatitis (ulcers/erosions/blisters of oral mucosa and lips) and a rash?

Answer 68

Paraneoplastic pemphigus

Question 69

What conditions are linked to paraneoplastic pemphigus?

Answer 69

Non-hodgkins and Castlemans disease (produces the autoantibody)

Question 70

What condition shows concentric erythematous lesions?

Answer 70

Erythema gyratum repens

Question 71

What is the other name for Werewolfs syndrome?

Answer 71

Acquired hypertrichosis lanuginosa

Question 72

What is seen in acquired hypertrichosis lanuginosa?

Answer 72

Acute onset of lanugo hairs at face and body

Question 73

What can cause acquired hypertrichosis lanuginosa?

Answer 73

Acquired hypertrichosis lanuginosa - often associated with metabolic and endocrine disorders and use of certain drugs. Also seen in eating disorders

Question 74

What condition causes eruptive seborrhoeic keratosis?

Answer 74

Leser-Trélat

Question 75

What is Leser-Trélat linked to?

Answer 75

GI adenocarcinomas

Question 76

What condition causes psoriasiform changes of hands, feet, ears, and nose, with involvement of the nails and periungual tissues?

Answer 76

Bazex syndrome

Question 77

What syndrome causes tanned skin and hyper pigmentation of the oral mucosa?

Answer 77

Ectopic ACTH syndrome