SKIN MANIFESTATIONS OF

SYSTEMIC DISEASES

Window to many internal diseases

Mirror to many internal diseases

Grouped in various ways

1. By disease category e.g. cancers & skin
II. By organ system involvement e.g. skin & gut
III. By pathogenic mechanisms e.g. collagen
vascular disease
IV. On basis of characteristic reaction pattern e.g.
Erythema nodosum

By disease category
SKIN CHANGE

UNDERLYING CANCER

Acanthosis nigricans Adeno Ca stomach,

lung,ovary,pancreas,colon

Acanthosis Nigricans

ACANTHOSIS NIGRICANS
characterized by
symmetric, velvety to
verrucous,
hyperkeratotic and
hyperpigmented
plaques with a
predilection for the
axillae, nape and other
flexural areas.

SKIN CHANGE
CANCER

UNDERLYING

Dermatomyositis NPC, Ca breast,

lung etc

Dermatomyositis

SKIN CHANGE
CANCER
Erythema
tongue/
gyratum

repens

UNDERLYING

Ca breast/cervix/
hypopharynx

Erythema
gyratum repens

Necrolytic Migratory Erythema (NME)

SKIN CHANGE
CANCER

UNDERLYING

Acquired ichthyosis Lymphomas,

solid
organ tumours

Generalised pruritus
Lymphomas,
Ca
stomach, lung

Erythroderma
Lymphomas, Solid
organ tumours

SKIN CHANGE
CANCER

UNDERLYING

NME (necrolytic
Glucagonoma
migratory
(islet cell tumor)
erythema

Icthyosis

Erythroderma

SKIN CHANGE
CANCER

UNDERLYING

Pachydermoperiostitis Ca lung,
uterus,
bronchiectasis
lung abscess

Bowens (unexposed) Squamous

cell
carcinoma

Herpes zoster

Cancers & Skin

Lymphomas/Leukaemias/Myeloma

a. Specific

infiltrates

b. Non-specific
herpes
pigmentation
pruritus
purpura

Genetic syndromes

1. Palmoplantar
keratoderma

Ca oesophagus

Genetic syndrome
Peutz-Jeghers
Malignant
transformation
syndrome
of polyps of small
guts

Peutz Jegher syndrome

Genetic syndrome Underlying

Cancer

Gardners syndrome
Soft
tumours,osteomas,polyp

Dermatitis herpetiformis

Seborrhoeic warts (multiple Leser Trelat sign

eruptive)

Hyperpigmentation (MSH, Cushings, Ca thymus,

lung
ACTH-like peptides)
pancreas

Migratory thrombophlebitis Ca pancreas,

larynx, thyroid,
breast, lung, stomach, colon

Lymphoma gut

Eruptive seborrhoeic keratosis

Skin & endocrine / metabolic disease

Diabetes mellitus
Adrenal disease Cushings, Addisons disease
Lipids

Xanthomas

Thyroid disease hyper & hypothyroidism

Porphyrias

PCT, EPP, CEP

DIABETES MELLITUS

DM is a group of metabolic disorders

characterized by chronic hyperglycaemia
due to relative insulin deficiency,
resistance or both.

Associated with disturbances of

carbohydrate and lipid metabolism.

It is common and affects appx. 30 million

people worldwide.

In 1995, the National Cardiovascular Risk

Factor Prevalence Study in Malaysia
showed that 7.7% of the adult population
suffer from DM.

95% have type -2 DM

Common among all ethnic groups

especially Indians.

At least 30 % of diabetics have cutaneous

involvement during the course of the
disease.

Cutaneous Manifestations of Diabetes

Mellitus
Classified into 4 categories:

Cutaneous diseases associated with

diabetes mellitus.

Cutaneous infections

Cutaneous manifestations of diabetic

complications

Skin reactions to diabetic treatment.

NECROBIOSIS LIPOIDICA DIABETICORUM

NLD
Waxy,tan plaque on shin.
Telangiectatic atrophic
centre.
Solitary or multiple.
85%-90% on lower
extremities, especially
pretibial areas.
When NLD occurs in areas
other than the legs, it is
less commonly associated
with DM.

NECROBIOSIS LIPOIDICA
DIABETICORUM
(NLD)

Only 0.3% of all patients with DM will

have NLD.
Muller SA. Mayo Clin proc 1966

60% have DM and another 20%

showed glucose intolerance or a
positive family history.
Muller Sa. Arch Derm 1966

M:F ratio 1:3

NECROBIOSIS LIPOIDICA DIABETICORUM

(NLD)

3rd and 4th decade of life.

Associated with both IDDM and

NIDDM

It is independent of patients
glycaemic control.

TREATMENT

High- potency topical steroids to the active

margins may arrest the progression.

Others : aspirin, dipyrimadole

Diabetic
Dermopathy
Pathogenesis :
unknown
Treatment :
none

DIABETIC
DERMOPATHY
hyperpigmented
or atrophic
macules on the
shins

DIABETIC
DERMOPATHY
(shin spots)
.
Found in 3060%.
Atrophic,hyper
pigmented,ova
l/round areas
distributed
bilaterally but
not
symmetrically.

Diabetic
Dermopathy.
Histology:
Early lesions : oedema
of papillary
dermis,extravasated
RBCs and mild
lymphocytic infiltrate.
Older lesions :Thick
walled capillaries in
papillary dermis and
extravasated RBCs

GRANULOMA
ANNULARE

Diabetic Thick Skin

3 Forms :

Scleroderma- like syndrome

Generalized thick skin
Sclerederma adultorum of Buschke

Scleredema adultorum of Diabetes Mellitus

Characterized by marked increase in dermal thickness

over upper back and upper neck in middle-aged,
overweight, poorly controlled type-11 diabetic.

2.5% in patients with type-11 diabetics.

Lierbeman et al reported decrease skin thickness with

tight blood sugar control and insulin administration.

No known treatment for diabetic sclerederma.

Knuckle pebbles
Thickening of the skin
on the dorsum of the
hand can be due to
many causes, including
DM. with pebbling of
the skin on the knuckle
area.
30% of diabetics have
hand skin thickening.
Significance?
Literature suggests
that digital sclerosis is
a marker for retinal

DIABETIC BULLAE
Adult onset diabetics
may have
spontaneous onset of
multiple bullae on
lower extremities.
These lesions may not
secondary to trauma
or infection.
Spontaneous healing
occurs within 2-5
weeks.

Diabetic Bullae
3 types:

Spontaneous and non-scarring type:

- commonest, heals spontaneously within 2-5 weeks
- intraepidermal cleavage without acantholysis.

Haemorrhagic and heals with atrophic scarring:

- cleavage below DEJ and destruction of anchoring fibrils

Multiple tender nonscarring blisters in sunexposed and deeply tanned skin :

- cleavage plane at lamina lucida

Diabetic

Bullae.
Clear fluidfilled bullae
on the
distal 1/3rd
medial
surface of
left LL.

Syndrome of Insulin
Resistance

Acanthosis
nigricans

Yellow Nails
Diabetics tend to have yellow nails.Lithner et al.Acta Med Scand
200.1976

Can occur in all nails but esp. on the distal end of the nail of
the hallux.

Salt and pepper

hyperpig-mentation
on shins with no
atrophy
Common in elderly
diabetics.
Due to RBC
extravasation in
superficial plexus.
(Cayenne pepper
spots)

Eruptive Xanthomas
Lipid abnormality-Type 1
increase in TG/VLDL, glycosuria
and hyperglycaemia.
sudden onset of crops of
nonpruritic, nontender, firm
yellow papules,each with an
erythematous rim.
extensor surfaces-knees,
elbows, back,buttocks and
trunk.

Eruptive Xanthomas

Lesions resolve
when CHO and lipid
metabolism
controlled.

HPE :
lipid laden
histiocytes and
mixed lymphoneutrophilic
inflammatory
infiltrate in dermis

Kyrles
Disease:
an uncommon
finding in patient on
renal dialysis.

Kyrles disease
Reactive perforating

collagenosis
characterised by

hyperkeratotic follicular
and perifollicular papules
Transepidermal

elimination of dermal
material that may
represents altered collagen

DIABETIC NEUROPATHY
Distal symmetrical neuropathy with mixed motor and sensory nerve involvement.

dorsally
subluxed
digits,
distally
displaced
plantar fat
pads,
depressed
metatarsal
heads,hammer
toes
and pes cavus.
A painless and

Gangrene in
Diabetes.
Hyperglycaemia
can allow usually
nonpathogenic
organisms to
establish an
infection in
traumatized skin.
Occasionally
resulting in
gangrene and
loss of limbs.

Chronic candidiasis of the fingernails.

Although dystrophic nails are often
thought to be the result of dermatophyte
infection, nail plate cultures show
Candida species in 5% of the time.

Fat hypertrophy
secondary to repeated
insulin injection.

Thyroid disease
Hypothyroidism

Hyperthyroidism

Skin - cold, dry, thickened, scaly

sweaty, miliaria

Hair - diffuse alopecia, thick, coarse

soft
Generalised pruritus

diffuse alopecia/fine/

generalised pruritus

Carotenemia
pigmentation,
melasma, vitiligo
Onycholysis
Urticaria
Pretibial myxoedema
acropachy

By organ system involvement

1. Skin & gut
2. Skin & kidney
4. Skin & liver

1. Skin & the gut

GI bleeding

Henoch schonlein purpura,

Hereditary haemorrhagic
telangiectasia

Polyposis

Peutz-Jeghers, Gardners,
Cronkhite-Canada syndromes

Liver cirrhosis
Wilsons disease, Primary biliary
cirrhosis, Haemachromatosis
Retroperitoneal
Haemorrhage

Pancreatitis periumbilical bruising

(Cullens sign)
- flank bruising
( Grey Turners sign)

Hereditary Haemorrhagic Telangiectasia

2. Skin & the kidney

Renal Failure
Xerosis, urea frost
Pigmentation face, hands
Generalised pruritus
Purpura
Gynaecomastia

Types of Interactions - Liver &

Skin
1.

Skin manifestations of liver diseases

2.

Liver abnormalities caused by skin

diseases

3.

Both skin & liver involved in same

systemic disease

4.

Hepatotoxicity of dermatological drugs or

adverse cutaneous reactions to drugs
used for liver diseases

Skin Manifestations of Liver

Diseases

Jaundice
Pruritus
Pigmentary changes
Vascular changes
Purpura
Nail changes
Xanthomas
Dupuytrens contracture
Hormonal effects

Viral Hepatitis (A,B,C)

Porphyrias (PCT)
Alcoholic liver disease
Malignant carcinoid
syndrome (flushing)
Necrolytic migratory
erythema (NME)
Alpha-1 antitrypsin
deficiency (panniculitis)
Autoimmune
hepatitis(AIH)

Palmer Erythema

Kayser- Fleischer ring

Spider Telangiectasia

Terrys (white) Nails

Viral Hepatitis & the Skin

Hepatitis A
Hepatitis C

Hepatitis B

Jaundice
* Polyarteritis nodosa
* Mixed
Croyoglobulinemia
Urticaria
* Papular acrodermatitis * Porphyria
(PCT )
Exanth rash
of childhood (PAC)
*
Leucocytovasculitis vasculitis
Cut vasculitis
Serum sickness-like
* Lichen
planus
Cryoglobulinemia
syndrome
Polyarteritis
nodosa
Erythema nodosum
Sjogrens
syndrome
Urticaria
Behchts
syndrome
Mixed cryglobulinemia
Necrolytic
migratory
erythema

Polyarteritis Nodosa ( PAN ) & HBV

Up to 50% of people with PAN are HBsAg +ve

10 20% have cutaneous involvement

Lesions include : palpable purpura

vasculitic ulcers
tender nodules
livedo reticularis
urticaria / angioedema
distal gangrene

No correlation with severity of liver involvement

Treatment include : corticosteroids, immunosuppressives

(cyclophosphamide), cyclosporin, plasma exchange

Skin in Polyarteritis Nodosa (PAN)

Livido reticularis

Vasculitis causing skin infarction

Leucocytoclastic vasculitis

Skin in Polyarteritis Nodosa (PAN)

Pyoderma GangrenosumTopical Cyclosporin Treatment

Papular Acrodermatitis of Childhood

(Gianotti Crosti Syndrome) & HBV

Children 2-6 years

Clinical features :
non relapsing papular dermatitis
face and limbs , spares trunk
lymphadenopathy
acute hepatitis (mostly anicteric)
HBsAg antigenaemia
hepatitis can progress chronic liver
disease
dermatitis resolves in 4 weeks

Papular Acrodermatitis of Childhood PAC

Gianotti Crosti Syndrome & HBV

Papular lesions on Face, limbs

Mixed Cryoglobulinemias & HCV

30 50 % of patients with HCV have circulating

cryoglobulins

60 -100 % of patients have skin findings

palpable purpura
livedo reticularis
acrocyanosis
urticarial plaques
ulcerations

Dermatol Clin 20 (2002) 449-458)

Cryoglobulinemia in HCV

Livido Reticularis

Cryoglobulins

Vasculitis

Reticulate Plaques

Palpable Purpura

Leucocytoclastic Vasculitis

Lichen Planus & HCV

Papular LP

Erosive oral Lichen planus

Porphyria Cutanea Tarda (PCT) & HCV

PCT seen in 62% of patients with HCV

Presents as : tense bullae
vesicles
erosions
heals with scarring & milia
Lesions on sun exposed skin
Complain of fragility of skin
Mechanism : decrease uroporphyrinogen decarboxylase
activity

Dermatol Clin 20 (2002) 449-458

Porphyria Cutanea Tarda & HCV

Alpha-1-antitrypsin associated
Panniculitis ( lung, liver,renal, GIT )

The Skin in
Malignant Carcinoid Syndrome

10 % of patients with carcinoid tumour

Symptoms when liver involved with metastasis
mediators escape into circulation
Cutaneous features :
flushing (nearly all cases)
pellagra (niacin deficiency)
scleroderma (a variant, lower
limbs, heart)
pruritus
rosacea
skin metastasis
British Journal of Dermatology 2005 152, pp 71-75

Cutaneous Manifestations of
Alcohol Abuse

Spider
telangiactasias
Palmer erythema
Caput madusae
Flushing
Jaundice
Pruritus
Urticaria
Plethoric facies

Koilonychia
Terrys nail
Clubbing
Hyperpigmentation
Black hairy tongue
Glossitis
Leucoplakia

Jaundice
Clubbing
Ascites
Dupuytrens
Contracture
Gynaecomastia

Leuconychia

By pathogenetic mechanism
Collagen vascular disease
Lupus Erythematosus
Systemic sclerosis
Dermatomyositis

Lupus erythematosus
CCLE

Discoid lesions

SCLE

Psoriasiform, annular / polycylic

ACLE

Malar / butterfly erythema, photosensitive

dermatoses, mouth ulcers, DLE lesions,
alopecia, purpura, vasculitis, urticarial vasculitis,
livido reticularis, bullae, erythema multiforme,
gangrene fingers / toes (Raynauds), periungal
nail
fold telangiectasia, subcutaneous nodules/
plaques,
panniculitis), scleroderma-like changes,
erythromelalgia, poikiloderma

Neonatal CHB, annular / polycyclic lesions

Systemic sclerosis
Thickening sclerosis - hands, forearms, arms, face, chest
(beak-like mouth, pinched nose)
Raynauds phenomenon
Pigmentation diffuse, or hypopigmentation
Nail fold erythema / telangiectasia
Fingertips, knuckles - vasculitis/ulcers/gangrene/atrophy
Face matt-like / papular telangiectasia
Paronychia
Leg ulcers
Palma erythema
Calcinosis cutis hands, elbow, iliac crest, spine
Poikiloderma

Dermatomyositis
Face
Nail fold

peri-orbital heliotrope rash / oedema

periungal erythema / telangiectasia,
cuticular hyperkeratosis
Knuckles
Gottrons papules
Photosensitivity
Poikiloderma
Raynauds phen
Urticaria, EN, EM
Violaceous follicular papules.

Dermatomyositis

On basis of characteristic reaction pattern

Pruritus
Erythema & annular erythema
Petechiae, purpura, vasculitis
Urticaria
Erythema multiforme, TEN
Subcutaneous nodules of leg EN
Asymptomatic nodules/plaques
Dermatitis
Erythroderma
Ichthyosis
Psoriasiform lesions
Papular, acneiform & nodular lesions
Yellow nodules & plaques
Bullous lesions
Leg ulcers
Pigmentary disorders
Nails, hair

Thank You

Pruritus
Localised

Genital itch ( candidiasis ) - DM

Generalised

Primary skin disease

Secondary systemic disease
Malignancy lymphomas
Leukaemia / CA
Liver obstructive jaundice
Renal uraemia
Fe-deficiency anaemia
PRV

Disorders of Pigmentation
Vitiligo

Autoimmune disorders thyroid dis, Addisons dis.

Brown pigmentation (CALM) Neurofibromatosis

Perioral lentigo, int. polyp Peutz-Jeghers
Flexural, thickened, skin tagsDM, Ca (stomach)
Diffuse, brown
with grey-brown hue

Haemochromatosis

With bulla, hypertrichosis PCT

scars, exposed parts
Hypo with hyperpigmentation

Scleroderma

Erythema
Widespread / prodromal symptoms viral rash
Localised face butterfly
LE
violaceous / heliotrope
Dermatomyositis
Pigmentary changes/dermal sclerosis
/nail fold telangiectasis
Scleroderma
Nasolabial, eye involvement, periodic
flushing
Rosacea, menopause
Periodic flushing, asthma, abd. pain
Carcinoid syndrome
diarrhoea
Palmar erythema
Pregnancy, liver dis.,
SLE, RA,
hyperthyroidism

Erythema
Annular
eythema annulare centrifugum
Infection, infestation,
Malignancy, SLE
Erythema gyratum repens

Malignancy

Petechiae, purpura
(Platelet/Vascular/Coagulation)
Infection
Septicaemia meningococcal, gonococcal
DHF
Scurvy
Cushings syndrome
Drugs

Vasculitis
Primary
Secondary
Drugs
Infections - Strep, HBV, EBV
Collagen - SLE, RA, Dermatomyositis
Cryoglobulinaemia
Lymphoma / leukaenia

Urticaria
Ordinary
Acute (< 6 wks) Food, drugs, infection parasite, strep
Chronic (>6 wks) Food, drugs, infection, SLE, malignancy
thyrotoxicosis, psychologic
Physical
UVL
EPP, CEP
Cold
Cryoglobulinaemia, (myeloma, collagen,
CA, syphilis)
Urticarial
vasculitis

SLE, Lymphoma, HBV

(> 24 hours, pain

Pigmentation)

Contact

Erythema Multiforme
Infection HSV (recurrent EM)
Strep, superficial & deep mycoses
Trichomoniasis, Mycoplasma
Drugs
Collagen vascular disease
Radiotherapy
Malignancy

Toxic Epidermal Necrolysis

Infection - Staph (SSSS-children), virus
Radiotherapy
Lymphoma, Ca
Drugs

Subcutaneous (painful nodules ) of legs

Erythema nodosum Infection Strep,TB, Leprosy
Chlamydia, Yersenia,
deep mycoses, virus
Drugs
OCP, Sulphonamide
Sarcoidosis
Inflammatory bowel dis. Crohns
Behcets disease, CA
Erythema induratum TB
Nodular vasculitis
Strep, ? TB, drugs, Collagen dis.
Polyarteritis nodosa Possible systemic involvement
Panniculitis
Pancreatic dis, Collagen dis,
Trauma, Foreign body, Malignancy
Subacute nodular
migratory panniculitis ? Trauma, OCP, idiopathic

Non tender nodules

Leprosy
Malignancy

Sarcoidosis

lymphomas, leukaemias
multiple myeloma, MF,
secondaries

Eczema / Dermatitis
Seborrhoeic, petechiae, purpura Letterer Siwe
papules
(Histiocytosis X)
Seborrhoeic, diarrhoea, infection Leiners dis ( C5 defy)
Seborrhoeic, atopic, infections
purpura
Atopic, hypomelanosis, MR
Photodermatitis
PCT

Wiskott Aldrich syn

Phenylketonuria

LE, Dermatomyositis,

Exfoliative dermatitis (Erythroderma)

Skin disease eczema, psoriasis
Drugs

sulphonamides, phenytoin, allopurinol

Malignancies Lymphoma, leukaemia, MF, Ca

Idiopathic

Ichthyosis
Congenital
Acquired

Vulgaris, Sex-linked, CIE

Lymphomas, leprosy, drugs, HIV,
uraemia, malabsorpton,
hypothyroidism

Psoriasiform
Psoriasis
Reiters disease
Secondary Syphilis
Lupus erythematosus - SCLE
Malignancy
Drugs

Papular, acneiform, nodular ( face )

Acneiform, hirsutism, menstrual Endocrine dis, CA
irregularity
Adenoma sebaeceum, epilepsy, Tuberous sclerosis
MR, shagreen patch, periungal
fibroma, ash-leaf hypopig. macule
Cobblestone, lichenoid papules Thyroid adenoma,
CA / fibrocystic breast
Epidermal cyst, fibroma, bone
osteoma, & colonic polyposis

Gardners syndrome

Neurofibromas, CALMs, Lisch

Neurofibromatosis

Yellow nodules & plaques

With hyperlipidaemia, DM Xanthoma, xanthelasma
Nephrotic syndrome, biliary (familial hypercholesterolemia
cirrhosis, hypothyroidism /hypertriglyseridemia, broad
beta dis, lipoprotein lipase
deficiency)
Normolipidemia

Plane xanthoma, myeloma

lymphoma, Ca

With angioid streaks, loss of Pseudoxanthoma elasticum

central vision, int. claudication,
angina pectoris, GI bleed

Bullous diseases
Congenital
Acquired
Drugs

Stevens-Johnson syndrome
FDE

Autoimmune Dermatitis herpetiformis

(a/w gluten sensitive enteropathy)
Pemphigus can be a/w thymoma, Ca
SLE, PA

Non infective granulomas

Red papule, plaque, annular Sarcoidosis
with systemic involvement
Red papules arranged in rings
( a/w DM )

Granuloma annulare

Red yellow atrophic plaque Necrobiosis lipoidica

with telangiectasia, over shins ( a/w DM )

Leg ulcers
Stasis

Venous disease

Vasculitis

Collagen vascular disease, PAN, HSP

Infective
Malignant
Neuropathic
Leprosy, DM, tabes dosalis,
syringomyelia, polyneuropathy
Others

Pyoderma gangrenosum

Nails
Colour
- brown
chronic renal failure
yellow, oedema, pul infection, yellow nail syndrome
effusion
- half moon
Wilsons disease
Onycholysis

Hyperthyroidism
psoriasis, pellagra

Koilonychia

Fe def. anaemia,
trauma

Periungual telangiectasia

LE, Dermatomyositis

Hair
Scarring
LE, Scleroderma, Lichen plano-pilaris, Infection,
Pseudo-pelade
Non scarring
Diffuse
LE, Fe defy, Hypopituitarism,
thyroid disease
Focal

Alopecia areata

Drug eruptions
1.
2.
3.
4.

Exanthem, morbilliform
Ampicillin, penicillin
Fixed drug eruption
Tetra, sulpha
Urticaria
Penicillin, aspirin
SJS, TEN
Sulpha, allopurinol
anti-convulsants
5. EM
Sulpha, barbiturates
6. Vasculitis
Allopurinol, thiazide
7. Pigmentation
OCP, clofazimine

Drug eruptions
8. Pruritus

Anti-depressants, CNS
stimulants
9. Psoriasiform
B-blockers, Li, gold,
anti-malarials
10. Acneiform
Steroids, anti-epileptic
11. Photosensitivity
Hydrallazine, isoniazid,
hydantoins, OCPs,
thiazides
12. Alopecia
Heparin, cytotoxic,
neomercazole
13.Lichenoid
Anti-malarials, PAS,
gold
14.EN
OCPs, sulpha

THANK YOU