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Skin in Systemic Disease
Digital Lecture Series : Chapter 20
Dr. NIRMAL B.
Assistant Professor,
Christian Medical College, Vellore.
CONTENTS
 Skin in nutritional disorders
 Skin in metabolic disorders
 Skin in heritable diseases
 Skin manifestations of blood disorders
 Skin manifestations of internal organ disorders
 Skin in connective tissue disorders
 Skin in vascular and inflammatory disorders
 MCQs
 Photo Quiz
Cutaneous manifestations of systemic diseases
 Skin mirrors many internal diseases which are often first noticed due
to cutaneous manifestations. Skin involvement is an integral part of
many systemic illnesses.
 Few systemic diseases with classical cutaneous manifestations are
discussed.
Skin in nutritional disorders
Physical signs of nutritional disease
 Alopecia
•
Anorexia, Bulimia, Marasmus
•
Biotin, Essential fatty acid, Iron deficiency
 Follicular hyperkeratosis
•
Essential fatty acid deficiency
•
Vitamin A, B, C, E deficiency
 Hyperpigmentation
•
Kwashiorkar
•
Vitamin B12 deficiency
•
Iron overload
Skin in nutritional disorders
 Hypopigmentation
•
Kwashiorkar
•
Biotin, Copper deficiency
 Seborrheic dermatitis
•
Riboflavin, pyridoxine deficiency
 Periorificial dermatitis
•
Biotin, Essential fatty acid, Zinc deficiency
 Acral dermatitis
•
Zinc deficiency
 Photodistributed dermatitis
•
Niacin deficiency
Pellagra
 Cellular deficiency of niacin resulting
from inadequate dietary supply.
 Rare causes are carcinoid tumour,
Hartnup disease and isoniazid therapy.
 Classical triad of clinical features is
dermatitis, diarrhoea and dementia.
 Skin changes resemble sunburn and
there is often characteristic well marginated eruption on neck called
‘Casal’s necklace’.
 Treatment : Oral niacinamide 0.5 g/day.
Acrodermatitis enteropathica
 Autosomal recessive disease due to
reduced zinc absorption.
 Typically starts after weaning or earlier if
the infant is not given breast milk.
 Acute eczematous erosive dermatitis
involving acral, perioral & anogenital
areas.
 Oral zinc dose of 2–3 mg/kg/day cures
all clinical manifestations apart from
hair and nail growth within a few days.
Skin in metabolic disorders
 Porphyrias
 Amyloidosis
 Xanthomatosis
Porphyrias
Cutaneous disease only
 Porphyria cutanea tarda
 Congenital erythropoietic porphyria
 Erythropoietic protoporphyria
Cutaneous disease & acute attacks
 Hereditary coproporphyria
 Variegate porphyria
Acute attacks only
 Acute intermittent porphyria
Porphyria cutanea tarda
 Due to uroporphyrinogen decarboxylase deficiency.
 Age of onset : 3rd or 4th decade.
 Clinical features : vesicles, bullae in areas of repeated trauma
healing with milia & scarring, hypertrichosis, sclerodermoid plaques.
 Treatment : Photoprotection, Phlebotomy, low dose chloroquine 125
mg twice weekly.
Amyloidosis
Classification of systemic amyloidosis
 Primary systemic amyloidosis
 Secondary systemic amyloidosis
 Dialysis related amyloidosis
 Inherited systemic amyloidosis
Systemic amyloidosis
Primary systemic amyloidosis
 The fibrils compose of protein AL amyloid due to plasma cell
dyscrasia.
 Age of onset in 6th decade with slight male preponderance.
 Clinical features : Macroglossia, Carpal tunnel syndrome,
hepatomegaly, edema, leg claudication, weight loss.
 Cutaneous features : Post-proctoscopic palpable purpura, waxy
purpuric papules, scleroderma like infiltration, nail dystrophy.
Systemic amyloidosis
Secondary systemic amyloidosis
 The fibrils are composed of AA protein.
 Causes : Rheumatoid arthritis, psoriasis, lepromatous leprosy,
venous ulcer, hidradenitis suppurativa, acne conglobata.
Dialysis related amyloidosis
 The fibrils are composed of β2 microglobulin.
Inherited systemic amyloidosis
 Muckle-Wells syndrome, Familial mediteranean fever,
Heredofamilial amyloid polyneuropathy.
Xanthomatoses
 Term xanthoma derived from Greek word ‘xanthos’ meaning yellow.
 Types : Tendon, Tuberous, Xanthelasma, Palmar, Planar, Eruptive.
Tendon xanthoma
 Occur commonly over extensor tendons over knuckles &
tendoachilis.
 Seen in familial hypercholesterolemia, sitosterolaemia,
cerebrotendinous xanthoma.
Tuberous xanthoma
 Occur over extensor aspect of elbows
& knees.
 Seen in Type III hyperlipoproteinemia.
Xanthelasma palpebrarum
 Occur over upper eyelids & around
medial canthus.
 Seen in normolipemics, Familial
hypercholesterolemia (Type II), Type
III hyperlipoproteinemia.
Xanthelasma
Palmar xanthoma
 Occur over palmar creases
 Pathognomonic of Type III hyperlipoproteinemia
Planar xanthoma
 Wide based, flat & wide spread
 Seen in paraprotrinemias
Eruptive xanthoma
 Multiple small papules affecting the extensors predominantly
 Seen in hypertriglyceridemia (Type I)
Skin in heritable diseases
 Neurofibromatosis
 Tuberous sclerosis
Multiple neurofibromas
Ash leaf macule in
Tuberous sclerosis
Neurofibromatoses (NF)
 Autosomal dominant inheritance with complete penetration.
 Gene for NF1 located in Chromosome 17.
 Criteria : Presence of two or more of the following
•
Six or more café-au-lait macules of over 5 mm in greatest
diameter in pre-pubertal individuals and over 15 mm in greatest
diameter in post-pubertal individuals.
•
Two or more neurofibromas of any type or one plexiform
neurofibroma.
•
Freckling in the axillary or inguinal regions.
•
Optic glioma.
Contd…
Neurofibromatoses (NF)
•
Two or more Lisch nodules.
•
Sphenoid dysplasia or thinning of long bone cortex with or
without pseudoarthrosis.
•
A first-degree relative with NF1.
Tuberous sclerosis
 Autosomal dominant inheritance.
 Diagnostic clinical triad : Epilepsy, Low Intelligence, Adenoma
sebaceum (Epiloia).
Cutaneous features
 Angiofibroma : discrete red-bown papules around naso-labial
furrows.
 Koenen’s tumour : periungual fibroma.
 Shagreen patch : skin coloured plaque in lumbosacral region.
 Ash-leaf macules : white ovoid macules over trunk or limbs.
Skin manifestations of blood disorders
 Leukaemia cutis
 Cutaneous Lymphoma
 Mycosis Fungoides
 Langerhans cell histiocytosis
Leukemia cutis
 Localized or disseminated skin infiltration by leukemic cells.
 Sign of systemic disease or relapse of existing leukemia.
 Commonly occurs in acute monocytic leukemia M5 and acute
myelomonocytic leukemia M4.
 Clinical presentation is variable but usually presents with pink or
violaceous papules and plaques.
Cutaneous lymphomas
 Skin is the second most common cause of extranodal lymphomas
after GIT.
 Classified as T-cell & NK cell and B-cell lymphomas.
 Mycosis fungoides is the most common cutaneous T-cell lymphoma
and represent 80% of all cutaneous lymphomas.
 Sezary syndrome is a leukemic variant of mycosis fungoides
characterized by a triad of erythroderma, lymphadenopathy and
circulating Sezary cells.
Mycosis fungoides
 Commonly occurs in late adulthood
with male predominance.
 Clinical stages include : patch, plaque,
tumor stage.
 Distribution favours non-sun exposed
areas (bathing trunk distribution).
 Variants include folliculotropic,
hypopigmented, pagetoid reticulosis,
granulomatous slack skin.
Langerhans cell histiocytosis
 Continuum of disorders considered reactive but have a broad
spectrum of severity.
 Cutaneous lesions vary from papules, vesicles, pustules, nodules,
ulcers involving head, trunk and skin folds.
 Associated with diabetes insipidus & exophthalmos.
 Systems involved include bones, lung and reticulo-endothelial
system.
Skin manifestations of internal organ disorders
 Disorders of endocrine system
•
Diabetes mellitus
•
Disorder of thyroid gland
•
Disorder of parathyroid gland
•
Disorder of adrenal gland
•
Disorder of sex hormones
 Disorder of renal system
 Disorder of gastrointestinal system
 Disorder of Liver
 Sarcoidosis
 Paraneoplastic dermatoses
Diabetes mellitus
Cutaneous changes in diabetes include :
 Acanthosis nigricans
 Diabetic dermopathy
 Necrobiosis lipoidica
 Limited joint mobility
 Scleredema diabeticorum
 Eruptive xanthomas
 Granuloma annulare
 Perforating disorders
 Bullous diabeticorum
 Bacterial & fungal infections
Acanthosis nigricans
 Grey-black velvety plaques
involving flexors.
 Tripe palms : palmar acanthosis
seen in malignancy.
Acanthosis Nigricans
Diabetic dermopathy
 Atrophic brown macules over
pretibial areas correlated with
duration and presence of end organ
complications of diabetes.
Necrobiosis lipoidica
 Yellow-brown plaque on anterior
pretibial region over time becomes
atrophic giving a glazed porcelain
sheen.
Diabetic Dermopathy
Disorder of Thyroid
 Graves disease is the commonest cause of hyperthyroidism
characterized by exophthalmos, thyroid acropachy and pretibial
myxedema.
 Cutaneous findings of hypothyroidism include dry skin, absence of
hair in the lateral third of eyebrow, myxedema due to accumulation
of mucopolysaccharides in the dermis.
Disorder of parathyroids
 Hypoparathyroidism :
•
Skin : dry, scaly, eczematous eruptions or exfoliative dermatitis.
•
Hair : thin, fragile, patchy alopecia.
•
Nails : atrophic, brittle with horizontal ridging
 Hyperparathyroidism :
•
Disabling pruritus in primary and secondary hyperparathyroidism
(due to chronic renal failure).
Disorder of Adrenal Glands
 Cushing’s Syndrome :
•
Skin : thin, fragile with purpura and
striae.
•
Redistribution of body fat :
Truncal obesity, moon facies, buffalo
hump and thin limbs.
•
Acne, hirsutism and acanthosis
nigricans.
 Addison’s Disease :
Generalised, diffuse brown-black pigmentation of skin and mucosae
 Accentuation of pigmentation on :
•
Exposed areas (face, hands, forearms),
•
Flexures (axillae, groins),
•
Bony prominences (knuckles, knees, elbows),
•
Normally pigmented areas (palmar creases, nipples, genitalia),
•
Pre-existing melanocytic nevi,
•
Frictional areas (e.g. beltline),
•
Mucosae (blue black colour especially over oral mucosa).
Disorder of sex hormones
 Excess :
•
Polycystic ovary syndrome, ovarian tumours, congenital adrenal
hyperplasia, Cushing’s disease, prolactinoma, drugs like
androgens, anabolic steroids or progestagens.
 Defeminising and virilising syndromes :
•
Hirsutism and male pattern alopecia
•
Thick, oily, hyperhidrotic skin; acne, acanthosis nigricans
 Deficiency :
•
Hypogonadism (Pituitary or non-pituitary)
•
Features of hypopituitarism
•
Absent or sparse axillary and pubic hair in males or female type
body hair distribution in males
Renal Disorder
 Renal failure :
•
Persistent generalised pruritus, dry, scaly skin.
•
Tendency to develop purpura/ecchymoses on minor trauma.
•
Half and half nails in chronic renal failure show brown red
discoloration of their distal half.
•
Pale yellow skin : associated anemia and pitting edema due to
accumulation of urochrome or carotene pigments.
•
Uremic frost : deposition of urea crystals on the nose and malar
area due to high urea levels.
•
Calcinosis cutis, pseudoporphyria cutanea tarda, nephrogenic
fibrosing dermatopathy.
Reno-cutaneous disease
 Systemic Lupus Erythematosus :
•
Discoid lesions, butterfly erythema, palatal ulcer, alopecia,
photosensitivity.
 Systemic Sclerosis :
•
Diffuse skin sclerosis, Raynaud’s phenomenon, telangiectasia,
pigmentation and calcinosis.
 Vasculitides (Henoch Schonlein, Wegener’s, Polyarteritis nodosa) :
•
Palpable purpura, vesicles, skin infarcts, ulcers.
 Lepromatous Leprosy :
•
Shiny papulonodules and diffuse infiltration of skin.
Gastrointestinal disorder
 Dysphagia :
 Bleeding :
Due to rashes that may extend
to esophagus
•
Hereditary haemorrhagic
telangiectasia
•
Infections
•
Blue rubber bleb nevi
•
Congenital and acquired
blistering diseases
•
Ehlers Danlos syndrome
•
Pseudoxanthoma Elasticum
•
Lichen planus
•
Kaposi’s sarcoma
•
Behcet’s disease
•
Stevens Johnson Syndrome
•
Dermatomyositis
Gastrointestinal disorder
 Abdominal pain :
• Herpes zoster
• Angioedema
• Porphyria
• Anderson : Fabry disease
• Vasculitis : Henoch Schonlein
purpura, Collagen vascular
diseases
• Polyposis : Gardner’s
syndrome, Peutz-Jeghers
syndrome, ulcerative colitis,
neurofibromatosis
• Ulcerative Colitis and Crohn’s
disease
• Pancreatitis
 Inflammatory Bowel Diseases :
• Pyoderma gangrenosum
• Aphthous ulcers
• Erythema Nodosum
• Malnutrition
• Rashes at ileostomy and
colostomy sites
• Metastatic cutaneous Crohn’s
disease
Liver disorder
 Pruritus
 Icterus
 Pigmentary changes
 Spider angiomas
 Palmar erythema
 Dilated abdominal wall veins
 Purpura
 Loss of body hair
 Gynaecomastia
 Peripheral edema
Sarcoidosis
 Sarcoidosis is a systemic granulomatous disease primarily affects
lungs but skin manifestations are seen often.
 Specific cutaneous lesions include
•
Translucent yellow-red papules,
•
Lupus pernio,
•
Angiolupoid lesions &
•
Subcutaneous nodules (Darier-Roussy sarcoid)
Sarcoidosis
 Lupus pernio are violaceous indurated plaques commonly involving
face and digits associated with upper respiratory tract disease.
 Erythema nodosum is the commonest non-specific finding and
heralds good prognosis.
 Histopathology is characterized by the presence of naked epitheloid
granuloma with paucity of surrounding lymphocytes.
Sarcoidosis
Paraneoplastic dermatoses
 Tripe palms :
•
Palmar ridges are accentuated mimicking mucosa of stomach.
•
Association : Lung and gastric carcinoma.
 Bazex syndrome :
•
Acral papulosquamous lesions with onychodystrophy.
•
Association : SCC of upper aerodigestive tract.
 Paraneoplastic pemphigus :
•
Severe refractory oral involvement.
•
Association : Non-Hodgkin’s lymphoma, Chronic lymphocytic
leukemia
Paraneoplastic dermatoses
 Erythema gyratum repens :
•
Wood grain pattened erythema
•
Association: Bronchial carcinoma
 Necrolytic migratory erythema :
•
Painful eroded crusted intertriginous and facial eruption
•
Association : Glucagonoma
 Hypertrichosis lanuginosa acquisita :
•
Non-pigmented languo hair over face & ears
•
Association : Lung, colon carcinoma
Skin in connective tissue disorders
 SLE
 Dermatomyositis
 Scleroderma
 Systemic sclerosis
 Rheumatoid Arthritis
 Sjogren’s syndrome
 Raynaud’s phenomenon
 Detailed in chapter 19, few salient aspects discussed
Lupus erythematosus
American Rheumatism Association criteria for diagnosis of systemic
lupus erythematosus
 Malar rash
 Discoid rash
 Photosensitivity
 Oral ulcers
 Non-erosive arthritis
 Serositis - pleurisy or pericarditis
 Renal disorder - persistent proteinuria (>0.5 g/day) or cellular casts
 Neurological disorder - seizures or psychosis
Lupus erythematosus
 Haematological disorder - haemolytic anaemia or leukopenia
(<4000/mm) or
lymphopenia (<1500/mm) or thrombocytopenia (<100 000/mm).
 Immunological disorder - LE cells or anti-DNA antibody or anti-Sm
antibody or
false-positive serology for syphilis (longer than 6 months).
 Antinuclear antibodies
# A patient is diagnosed to have SLE if 4 or more criterias are
fulfilled.
Cutaneous manifestations in LE
 Malar rash :
Fixed erythema over malar eminences
sparing nasolabial folds.
 Discoid rash :
Erythematous plaques with adherent
scaling and follicular plugging.
 Photosensitivity :
Skin rash as an unusual reaction to
sunlight.
 Oral ulcers :
Painless oral or nasopharyngeal
ulceration.
Malar Rash
Oral Erosion
Dermatomyositis
Disorder mainly affecting skin, muscle and
blood vessels
 Characteristic erythematous and
oedematous changes in the skin are
usually associated with muscle
weakness and inflammation.
 In childhood, diffuse calcinosis is
frequent.
 In adults, the disease is commonly
associated with underlying carcinoma or
lymphoma.
Scleroderma
ARA criteria for scleroderma
 Major criteria : Scleroderma proximal to the digits, affecting limbs,
face, neck or trunk; or
 At least two minor criteria :
•
Sclerodactyly
•
Digital pitted scarring
•
Bilateral basal pulmonary fibrosis.
Diffuse cutaneous systemic sclerosis
 Short interval (<1 year) between the onset of Raynaud’s
phenomenon and development of skin changes.
 Truncal and peripheral skin involvement.
 Tendon friction rubs.
 Pulmonary fibrosis, renal failure, gastrointestinal disease, myocardial
involvement.
 Capillary drop-out visible in nail folds.
 Scl-70 antibody-positive.
Limited cutaneous systemic sclerosis
 Long history of Raynaud’s phenomenon.
 Limited skin involvement at extremities only.
 Calcification, telangiectasia, late onset of pulmonary hypertension.
 Capillary dilatation visible in nail folds.
 Anticentromere antibody-positive.
Rheumatoid arthritis
 Rheumatoid nodules
 Rheumatoid vasculitis (RV)
 Felty’s syndrome
 Pyoderma gangrenosum (PG)
 Interstitial granulomatous dermatitis with arthritis
 Palisaded neutrophilic and granulomatous dermatitis
 Rheumatoid neutrophilic dermatitis
 Juvenile rheumatoid arthritis (JRA)
 Adult-onset Still’s disease
Sjogren syndrome
 Xeroderma
 SCLE-like rashes, annular erythema, Sweet’s-like lesions
 Raynaud’s syndrome
 Hyperglobulinaemic purpura
 Inflammatory vasculitis
 Vitiligo
 Abnormalities of sweating
 Amyloid
 Alopecia
Raynaud’s phenomenon
 Refers to digital ischemia provoked by cold exposure or emotional
stress.
 Classical triad of colour change :
Pallor, cyanosis and hyperemia but most describe only blanching
followed by numbness.
 Classified as primary (idiopathic) and secondary.
 Secondary causes include connective tissue disorders, obstructive
arterial disease, neurological diseases, drugs and hypothyroidism.
Skin in vascular and inflammatory disorders
 Cutaneous necrotizing vasculitis
 Systemic necrotizing vasculitis
 Wegener’s granulomatosis
 Churg Strauss disease
 Behcet’s disease
Cutaneous necrotizing vasculitis
 Palpable purpura is the characteristic lesion commonly involving the
lower extremities.
 Henoch-Schonlein purpura is the most widely recognized subgroup
of this entity characterized by a triad of colicky abdominal pain,
arthralgia and hematuria.
 Histologic findings include fibrinoid necrosis of blood vessels,
neutrophilic infiltration of vessel wall, endothelial swelling and
extravasated erythrocytes.
Systemic necrotizing vasculitis
Polyarteritis nodosa
 Characterized by necrotizing inflammation of medium-sized or small
arteries without glomerulonephritis.
Microscopic polyangiitis
 Systemic vasculitis affecting blood vessels ranging in size from
capillaries to medium-sized arteries.
 Symptoms include fever, weight loss, arthralgia several years before
onset of pulmonary and renal disease.
Systemic necrotizing vasculitis
Wegener’s granulomatosis
 Characteristic triad of systemic small vessel vasculitis, necrotizing
granulomatous inflammation of upper & lower respiratory tracts and
glomerulonephritis.
Churg-Strauss syndrome
 Characterized by asthma, peripheral blood eosinophilia and
necrotizing vasculitis with extravascular granulomas.
Behcet’s disease
International Study Group criteria for the diagnosis of Behçet’s disease
 Recurrent oral ulceration- at least 3 times in one 12-month period.
Plus two of the following :
 Recurrent genital ulceration.
 Eye lesions - anterior uveitis, posterior uveitis or retinal vasculitis.
 Skin lesions - Erythema nodosum, pseudofolliculitis, papulo-pustular
or acneiform nodules.
 Positive pathergy test.
MCQ’s
Q.1) Pellagra is characterized by a triad of clinical symptoms including all
except
A. Dermatitis
B. Dementia
C. Dysphagia
D. Diarrhoea
Q.2) Eruptive xanthomas are characteristically seen in which type of
familial hyperlipidemia?
A. Type I
B. Type II
C. Type III
D. Type IV
MCQ’s
Q.3) ___________ or more café-au-lait macules of over 5 mm in greatest
diameter in prepubertal individuals.
A. Two
B. Four
C. Six
D. Eight
Q.4) The sequence of events in Raynaud’s phenomenon are :
A. Pallor, Cyanosis, Rubor
B. Cyanosis, Pallor, Rubor
C. Rubor, Pallor, Cyanosis
D. Pallor, Rubor, Cyanosis
MCQ’s
Q.5) The following amine is one of the mediators of itch A. Serotonin
B. Epinephrine
C. Norepinephrine
D. Bradykinin
Photo Quiz
Q. Identify the clinical condition
Photo Quiz
Q. Identify the clinical condition
Thank You!