Systemic Disease

Question 1

Underlying systemic disease that have cutaneous manifestations

Answer 1

-Paraneoplastic phenomena
-Autoimmune conditions e.g. vitiligo, alopecia areata
-Connective tissue disease (lupus, vasculitis)
-Vascular disease (venous and arterial ulcers, lymphoedema)

Question 2

Examples of paraneoplastic phenomena

Answer 2

-Gorlin syndrome (basal cell naevus syndrome)
-Neurofibromatosis
-Tuberous Sclerosis?
-Peutz-Jeghers syndrome
-Acanthosis nigricans
-Acquired ichthyosis
-Pityriasis rotunda
-Leser-Trelat
-Sweet syndrome
-Dermomyositis
-Paraneoplastic pemphigus
-Hereditary haemorrhagic telangiectasia?

Question 3

Describe Neurofibromatosis

Answer 3

-Autosomal dominant, but new mutations frequent.
=Mutations of neurofibromin 1(NF1) or 2 (NF2) are associated with neurofibromatosis, but ‘peripheral’ NF is due to mutations of NF1

=Café au lait macules (more than 5 is abnormal)
=Axillary freckling
=Neurofibromas (with a characteristic soft, almost ‘negative’, pressure sensation).
=Flexiform large sub-cutaneous neurofibromas
=Lisch nodule (iris hamartoma)
=CNS tumours (e.g. gliomas) and tumours elsewhere

Question 4

Describe Tuberous Sclerosis

Answer 4

-Autosomal dominant

=Ash-leaf macules, oval areas of depigmentation, present at birth.
=Connective tissue nevi, known as shagreen patches
=Angiofibromas, commonly seen on the face (referred to incorrectly as adenoma sebaceum, as though they were sebaceous tumours)
=Periungual fibromas
=Seizures and cognitive impairment

Question 5

Describe Acanthosis nigricans

Answer 5

-Brown hyperkeratotic velvety / warty areas in the axillae, neck and the groins, and at other skin friction sites.
-The areas often develop multiple superimposed skin tags, and histologically resemble seborrhoeic keratoses.
-Internal malignancies are producing circulating growth factors affecting the skin’s frictional areas (in thin people)

=Acanthosis nigricans is also associated with insulin resistance, and is seen in obesity and type II diabetes (often called pseudo-acanthosis nigricans, but the skin features are identical)

Question 6

Describe Dermatomyositis

Answer 6

-Autoimmune disorder, much more common in women than men, characterised by a range of skin changes, and myositis.
-In adults, it is associated with an underlying malignancy in up to 50% of cases.

=Proximal muscle weakness before the rash, or vice versa.
=A violet/lilac (heliotrope) rash around the eyes
=Erythematous rash that sometimes appears in a photosensitive distribution although whether it is photosensitive is debated.
=Violaceous lichenoid rash along the dorsal surface of the hands and fingers (Gottron’s papules)
=Painful cuticles, and prominent nail fold capillaries

Question 7

Diagnosis and management of Dermatomyositis

Answer 7

-Skin biopsy shows changes similar to those seen in LE, and the serum creatine kinase may be raised.
-The ANA is positive in around 50% of cases.

-Find an underlying tumour at presentation, and if one is not found, to periodically keep looking.
-High dose prednisolone

Question 8

Describe Hereditary haemorrhagic telangiectasia

Answer 8

-Autosomal dominant disorder which, despite the name, is characterised not by telangiectasia but by small AV malformations that look like 1-3mm flat red spots.
-Lesions are common on the lips, oral and nasal mucosae, skin (especially hands), and GI tract.
-The cutaneous features become apparent in adult life.
-Frequently presents with nose bleeds. May lead to anaemia. In a patient with GI bleeding, look at the lips and hands!
-Osler-Weber-Rendu disease

Question 9

Describe Acquired ichthyosis

Answer 9

-Mutations in filaggrin gene (usually both alleles): vulgaris
-Diffuse polygonal scaling that tends to spare the flexures, keratosis pilaris, and hyperlinear palms.
-Associated with atopic dermatitis
-Reflects underlying malignancy, most commonly lymphoma
=Weight loss, night sweats
=Full exam and work up
=Occasionally secondary cause (drugs/ malnutrition)

Question 10

Describe Sweet’s syndrome

Answer 10

-Acute febrile neutrophilic dermatosis
-Present acutely with plaques or nodules, that to the uninitiated often look blistered due to the amount of oedema (blisters can occur, however).
-Lesions may be pustular.
-There may be associated arthralgia, and of course pyrexia.
-Pathergy as in pyoderma gangrenosum or Behcet’s may occur

-Pathology shows oedema in the high dermis, a prominent neutrophil infiltrate and possibly vasculitis.
-The diagnosis is largely clinical
-Feature of acute myeloid leukaemia
-Responds dramatically to prednisolone given over a few weeks

Question 11

Describe Pityriasis rotunda

Answer 11

-Rare disease characterised by round or oval scaly (sharply defined with dry ichthyosis-like scaling), pigmented patches that mainly occur on the trunk, arms and legs.
-Type I is seen mainly in oriental and black patients older than 60 years and is often associated with internal disease or malignancy.
=Liver and stomach cancer/ leukaemia, SCC, multiple myeloma

Question 12

Describe Leser-Trelat

Answer 12

-Abrupt appearance of multiple seborrhoeic keratoses that rapidly increase in their size and number.
-It is caused by an associated cancer and often occurs with malignant acanthosis nigricans
=Adenocarcinoma of stomach or colon

Question 13

What is vitiligo?

Answer 13

-Acquired focal loss of pigmentation due to (a presumed) immunological attack on some melanocytes in the skin (with or without hair follicle melanocyte involvement).
-Functional melanocytes are not found within the affected areas
-0.5-2% of the population, but the burden of disease is greatest in those with high constitutional skin colour because the visual contrast with the normal pigmented skin is greatest in this group.
-Can be genetic

Question 14

Clinical features of vitiligo

Answer 14

-Sharply demarcated macular areas of depigmentation
-Symmetrical
-The hair may lose pigment too
-On some occasions the disorder is limited to one or more body segments
-The genitalia, the mouth and eyes and hands are preferentially affected
-The disease may affect only a few percent of the body or spread to almost 100% coverage
-Association with some organ specific autoimmune disorders such as pernicious anaemia and Addison’s disease

Question 15

Differential diagnosis of vitiligo

Answer 15

-If present at birth the likely diagnosis is not vitiligo but piebaldism: an inherited pigmentary disorder that clinically resembles vitiligo in appearance, but is due to KIT gene mutations
-LSEA and pityriasis versicolor and pityriasis alba
-Leprosy: is the cutaneous sensation intact; are the depigmented areas raised around the edges?

Question 16

Treatment of vitiligo

Answer 16

-Some patients’ vitiligo resolves spontaneously without treatment
-The more extensive the disease, and the longer the course of active pigment loss, the worse the prognosis
-Topical steroids or calcineurin inhibitors are tried in many, and in those with dark skin phototherapy with PUVA or UVB may be used.
=The problem with phototherapy in those with pale skin, is that the normal skin will hyperpigment, and the contrast with the pale areas may end up greater at the end of treatment than before. If somebody has very dark skin this is not usually a problem
-In some centres epidermal transplants from one body site to a particularly sensitive site such as the face may be tried. Certain types of laser are claimed to help, too
-Expertly applied, or instruction in, camouflage may be useful
-Many patients are left with stable depigmented areas permanently. Such areas are more sensitive to UVR

Question 17

What is alopecia areata?

Answer 17

-Common, of unknown aetiology, and is usually characterised by sharply demarcated coin shaped areas of hair loss, and is common on the scalp or the beard area.
-Onset can be at any age but it is common in early adulthood or childhood.
-The characteristic, but sometimes hard to find, clinical sign is the presence of exclamation mark hairs in which the bulb of the follicle becomes the dot of the exclamation mark – this is seen in the broken hair stumps visible close to the scalp.
-Alopecia areata is non-scarring, and in the vast majority of patients the hair regrows normally.
-When the hair regrows it may be white but eventually will become darker.
-When the whole scalp is involved it is known as alopecia totalis and some unlucky individuals develop alopecia areata over the whole body (alopecia universalis) including the eyebrows and lashes.
-The more extensive the disease, the worse the prognosis.
-Autoimmune assault on the hair follicle?
=Associated with other organ specific autoimmune diseases such as autoimmune thyroid disease

Question 18

Treatment of alopecia areata

Answer 18

-Wait and see (as the prognosis is generally good)
-Topical corticosteroid injections
-Induction of contact allergic sensitivity which, for reasons that are not understood, may stimulate hair growth (sometimes quite dramatically)
-Early in the course of the disease, a short burst of systemic corticosteroids
-In severe cases, a wig may be the only choice

Question 19

Cutaneous presentations of lupus

Answer 19

-SLE
=Butterfly rash

-Discoid LE
=Scaly, red plaques most commonly on face and head, scarring and scarring alopecia, post inflammatory pigmentation, women >men, worsened by sun exposure
=Clinical suspicion, biopsy, potent topical steroids, antimalarials

-Subacute cutaneous LE
=Photosensitivity, scaly red plaques over face or upper trunk resembling psoriatic plaques/ annular lesions with central clearing, scarring uncommon
=Serology (anti Ro and La), biopsy, systemic corticosteroids, antimalarials

-Lupus tumidus
=Erythematous nodules (like urticaria but fixed), no scale, precipitated by phototesting

-Lupus profundus
=Deeper inflammation involving sub-cutaneous tissues

Question 20

What is vasculitis?

Answer 20

-Damage or destruction of the vessel wall secondary to an inflammatory process
-Classifications depends on
=Size of vessel affected
=Dominant cell type
=Whether the vascular inflammation is ANCA associated or immune complex.

Question 21

Pathogenesis of vasculitis

Answer 21

-Most common mechanism is deposition of immune complexes in the vessel wall leading to complement activation and activation of neutrophils with resulting damage to the vessel wall and an inflammatory reaction around the vessel.
-A variant of this is found in the ANCA positive vascular disease where IgG antineutrophilic cytoplasmic antibodies react with intracellular antigens on neutrophils and also activate neutrophils leading to an antibody dependent cellular cytotoxicity of the endothelial wall.

-At a clinical level, the main triggers to always think about with any vasculitis are
=Infections
=Drugs
=Underlying systemic inflammatory process (e.g. SLE, rheumatoid arthritis, ANCA positive vasculitis)

Question 22

What is Leucocytoclastic vasculitis?

Answer 22

-Most common type of cutaneous vasculitis seen in dermatology.
-Immune complex deposition leads to inflammation of the post capillary venules.
=The vessel wall is damaged with fibrin deposition, and neutrophils move out of the blood vessel into the surrounding skin.
=A remnant of polymorph nuclei is known as nuclear dust and gives the name (leucocytoclasis).
=Early on in the reaction immunoglobulin deposition may be demonstrated on histopathology

Question 23

Clinical features of Leucocytoclastic vasculitis

Answer 23

-Palpable purpura
=legs, but can involve any part of the body.
-Early in the course the lesions may not show purpura, but just erythema without being raised.
-Lesions at different stages of evolution may be present in the same individual at the same time.
-Lesions can vary from a couple of millimetres up to a couple of centimetres, and may be blistered, or even largely pustular.
-They may break down leaving painful ulcers.

-Causes
=Infections, such as hepatitis A, B or C, streptococci or mycobacterium
=Drugs, including beta blockers, penicillins and thiazide diuretics
=Malignancies, including chronic lymphocytic leukaemia, lymphoma and myeloma
=Small vessel vasculitides. Wegener’s, Churg-Strauss and polyarteritis nodosa may be associated with leucocytoclastic vasculitis
=Systemic diseases: including inflammatory bowel disease, SLE and Behcet’s syndrome

Question 24

Diagnosis and management of Leucocytoclastic vasculitis

Answer 24

-Clinical but a biopsy is usually appropriate.

-The legs are usually the worst affected areas and patients do better with bed rest, elevation of the legs and compression bandaging.
-Some people use highly potent topical corticosteroids.
-Systemic steroids appear to improve the resolution of the disease and dapsone is another alternative.
-Before prescribing systemic corticosteroids you need to be confident that the rash doesn’t represent septic vasculitis.
-The condition will resolve in the majority of patients over a period of 2-6 weeks.
-In a minority, the condition is chronic with a course punctuated by recurrent episodes of vasculitis

Question 25

Describe Henoch-Schonlein purpura

Answer 25

-Children under the age of 10 years
-Leucocytoclastic vasculitis characterised by the presence of IgA in the skin lesion, and particularly in the kidney.
-Usually there is a history of a preceding upper respiratory tract infection.
-The skin rash follows the infection by 2 to 3 weeks and patients develop joint pains, abdominal pain and, in 50%, renal disease.
-Assessment of renal function requires renal input and the abdominal pain reflects mesenteric vasculitis.
-The vasculitis in many patients resolves spontaneously with bed rest and supportive care, but any progressive renal disease may need to be more aggressively treated

Question 26

Describe septic vasculitis

Answer 26

-Rare, but fatal untreated
-Similar picture to leucocytoclastic vasculitis, often in young people.
-Patients are usually (but not always in the early stages) sick, the lesions often pustular with blistering and necrosis.
-Patients may be pyrexial with signs of damage in other tissues.

-Find, and treat the infection.
-Microorganisms, and thrombi in the post-capillary venules.
-There may be associated immune complexes.
-Gonococcus/ Sub-acute bacterial endocarditis/ Staphylococci, meningococci or fungi such as Aspergillus or Candida. Think hard about this diagnosis in patients who are immunosuppressed.

Question 27

What is Pyoderma Gangrenosum?

Answer 27

-Inflammatory lesion, commonly on the legs, very small and painful, which initially looks like an insect bite.
-This then becomes pustular and breaks down, leaving an ulcer with a red/purple edge.
-The ulcer grows in size, sometimes explosively, and is accompanied by pain.
-It may expose deep structures such as tendons and muscles.
-The edge may be undermined with gunmetal/blue coloured edges.
-It heals leaving cribriform scarring.
-The patients may be systemically unwell.

=large neutrophilic infiltrate with fibrin deposition in the vessels and leucocytoclasis. You may see evidence of vasculitis.

Question 28

Diseases associated with PG

Answer 28

-Inflammatory bowel disease
-Rheumatoid arthritis
-Ankylosing spondylitis
-Myeloma, IgA gammopathy
-Diabetes
-Chronic active hepatitis
-Primary biliary cirrhosis

Question 29

Diagnosis and treatment of PG

Answer 29

-Clinical diagnosis.
-Differential is of other causes of ulceration, including arterial and venous pathology, although they rarely cause diagnostic problems; and tumours.

-The mainstay of treatments are systemic corticosteroids and treatment of any underlying or associated diseases
=Topical corticosteroids are often used, although evidence is poor for efficacy.
-A variety of other immunosuppressive agents may be tried.
-Rarely the ulcer of PG is misdiagnosed as skin cancer and the lesion excised.
=The result is an even bigger ulcer

Question 30

What is erythema nodosum?

Answer 30

-Self-limiting panniculitis (inflammation of the fat) with painful red raised or indurated lesions most commonly on the lower legs in young adults.
-There is no ulceration and the epidermis appears intact.
-It is more common in females than in males.
-There may be malaise, pyrexia and arthralgia

Question 31

Potential triggers or associations of EN

Answer 31

-Drugs: Oral contraceptives, Penicillin
-Bacteria including streptococci, or mycobacterial
-Sarcoidosis
-Brucellosis
-Malignancies including lymphoma or leukaemia
-Inflammatory bowel disease
-Behcet’s syndrome

Question 32

Diagnosis and cause of EN

Answer 32

-NSAIDS often provide adequate relief and some degree of rest and compression stockings may help.
-Occasionally you will need to use systemic corticosteroids.
-Most patients only develop one episode but recurrences occasionally occur.

-Main differential is with a genuine nodular vasculitis (rare), which can present a similar picture (and is usually due to TB), or other rarer forms of panniculitis such as alpha-1 antitrypsin deficiency, or fat necrosis

Question 33

Clinical features of lymphoedema

Answer 33

-Feeling of tightness and heaviness in a limb
-Altered sensation, such as pins and needles, shooting pains or feeling of heat
-Joint discomfort due to the swelling, eg elbow, knee
-Tenderness in the groin of an affected leg
-Changes in temperature of the limb or affected skin (very thick with folds and bulges, cannot be lifted up or pinched/ dry warty spots on ankles and feet)
-Reduced range of movement

Question 34

Causes of lymphoedema

Answer 34

-Chronic venous insufficiency
-Surgery (removal of lymph nodes)
-Radiotherapy (scar tissue interrupts lymphatic flow)
-Accidental trauma, injury, infection (cellulitis): damages lymph vessels
-Reduced mobility
-Lymphatic filariasis

Question 35

Venous vs arterial ulcers

Answer 35

-Venous
=Above medial malleolus and below knee
=Painless
=Aching, swollen lower legs, feel uncomfortable when elevated
=Mottled red-brown staining, dry and itchy reddened skin
=Thickened skin, scaliness, papillomatosis, fissuring, oozing

-Arterial
=Feet, heels, toes
=Painful especially at night/ legs at rest and elevated
=Punched out borders
=Cold white or blueish shiny feet
=Intermittent claudication