Dermatologic Signs of Systemic Diseases5th yearLecture By Dr. Faraedon KaftanConsultant DermatologistCollege of MedicineUniversity of Sulaimani April. 10th2011

• The skin is often a window to systemic disease.• By recognizing cutaneous manifestations of systemic diseases,

the internist can often determine the appropriate diagnosis and therapy or the need for referral to a dermatologist.

1- Common cutaneous disorders (Seb D, Seb K, Urt,EM, V, EN)2- Blistering diseases (P, Pd, EBA)3- Internal malignancies (Cut. Metastases, Pag. Dis, AN, Amyloid)4- Cardiovascular disease (PXE, EDS)5- Pulmonary disease (Sarcoidosis)6- Rheumatic disease (Ps. A, LE, Sclerod., DM )7- Gastrointestinal disease (DH, ACE, LP …)8- Renal disease (Nephrogenic fibrosing dermopathy) 9- Endocrine and metabolic disease (Porphyria and Diabetes

Mellitus-Related Skin Conditions)

1- Common cutaneous disorders

Seborrheic dermatitis may be associated with systemic disease, such as 1-Parkinson's disease

2- (HIV: Human immunodeficiency virus ) infection. 3- (CVA: cerebrovascular accident ) can develop unilateral seborrheic

dermatitis on the scalp corresponding to the affected hemisphere, (The pathophysiology of this phenomenon is not completely understood.)

Seborrheic Keratoses• the most common benign cutaneous

neoplasms,

• are warty, age-related hyperkeratotic papules and plaques that appear anywhere on the body, most commonly the trunk.

• (Sign of Leser-Trélat):Rarely, if seborrheic keratoses appear suddenly in great numbers indicate an underlying adenocarcinoma of the GI tract

Urticaria or Hives

• are pruritic, edematous, evanescent wheals that resolve within 24 hours.• Acute urticaria typically lasts less than 6 weeks. • is most often caused by: 1- Medication (commonly penicillin or other antibiotics, sulfa drugs, aspirin) 2- Food (shellfish, nuts, chocolate), 3- infection: less often

Erythema Multiforme (EM)• Is a cutaneous hypersensitivity reaction characterized by Iris

(Target) lesions on the face, hands and feet. • is usually caused by: 1- Infection (herpes simplex virus or Mycoplasma pneumoniae) 2- and less commonly by drug sensitivity (sulfonamides,

barbiturates, antibiotics).

Vitiligo

• commonly occurs in periorificial areas (mouth, orbits, vagina, anus) or at sites of trauma (hands, elbows, knees).

• Vitiligo is often associated with: 1- Autoimmune thyroid disease, 2- diabetes mellitus (Insulin-dependent) 3- Pernicious anemia, or 4- Addison's disease.

Erythema Nodosum (EN)• Painful, erythematous nodules on the shins and occasionally elsewhere, in young

women, between 20 and 40 years, lasting an average of 3 to 6 weeks.• Causes of EN: 3 S + Tb1- Streptococcal pharyngitis is the most common . 2- Tuberculosis, 3- (GI) infections with Yersinia, Salmonella, or Shigella, and 4- Systemic fungal infections. 5- Less common causes: drug sensitivity (sulfonamides, salicylates, iodides, oral contraceptives

or hormone replacement therapy), and a variety of systemic diseases, most often inflammatory bowel disease (Crohn's disease more than ulcerative colitis) and sarcoidosis.

2- Blistering diseasesPemphigus Vulgaris

• painful mucosal erosions and flaccid skin blisters (bullae) that become erosive. occurs in the 40th to 60th of life,

• Mortality is significant, even with treatment.

Bullous Pemphigoid

• characterized by large, tense subepidermal blisters, which are often pruritic. Mucosal disease is rare.

• in the elderly, 65 and 75 years of age.

Epidermolysis Bullosa Acquisita: EBA

• uncommon bullous disease characterized by skin fragility, milia (small cysts), scarring alopecia, and nail dystrophy. primarily on the hands, feet, elbows, and knees.

• EBA may be associated with other autoimmune diseases, most frequently inflammatory bowel disease.

3- Internal malignancies

Cutaneous Metastases• Any malignant neoplasm can metastasize to the skin. • in men: Cutaneous metastases are from cancers of the

lung, large intestine, and kidney.• in women: Cutaneous metastases are from cancers of

the breast and large intestine.• Flesh-colored to violaceous nodules in close proximity

to the primary neoplasm; • Most common sites are the - Head (scalp), - Neck, and - Trunk.

Paget's Disease1- Mammary Paget's disease: Unilateral eczematous plaque of the nipple and areola. - is strongly associated with an underlying invasive Ca. of the breast

2- Extramammary Paget's disease: * persistent, eczematous plaque of the anogenital or axillary regions: * is often associated with an underlying - adnexal (apocrine gland) carcinoma or - cancer of the genitourinary tract or distal GIT.

Acanthosis Nigricans (ANs)

• smooth, velvet-like, hyperkeratotic plaques in intertriginous areas (e.g., groin, axillae, neck).

• Type I (Malignant AN): is associated with malignancy. May be adenocarcinoma of the GI tract (60% gastric)

• has a sudden onset and more extensive distribution, including the face, palms, and trunk.

• Type III AN is associated with obesity and insulin resistance and is the most commonly occurring type.

• AN can develop following the use of drugs: systemic Cs, nicotinic acid, diethylstilbestrol, and isoniazid (INH).

Amyloidosis

• Purpuric and Ecchymotic Papules on the eyelids and extremities due to amyloid infiltration in the vessels.

• may be a sign of multiple myeloma.

4- Cardiovascular diseasePseudoxanthoma Elasticum: PXE

• Brittle (Broken)and calcified elastic fibers. • Yellow papules over redundant skin folds

on the neck, abdomen, and groin, giving the skin the appearance of plucked chicken skin.

• Angioid streaks in Bruch's membrane of the eye.

Associated signs of PXE : 1- Hypertension (HTN) 2- Peripheral vascular and coronary artery

disease 3- Retinal and GI hemorrhage4- Stroke.

Ehlers-Danlos Syndrome: EDS

- abnormalities in collagen biosynthesis, which can affect multiorgans• Joint hyperextensibility, • Hypermobility (Hyperelasticity) • Skin and Vessel fragility, and • fish-mouth scars. * (7-11) types of EDS identified associated with: mitral valve prolapse, blue sclerae, vascular aneurysm, aortic

dissection, hernias, angina, GI bleeding (perforation), and peripheral vascular disease.

* Patients with vascular (type IV) EDS are prone to arterial rupture and have the highest mortality.

EDS

5- Pulmonary disease

Sarcoidosis• is a multisystem, granulomatous disease of the lungs, bones, CNS, lymph nodes, eyes, and skin. • more in women and in African Americans.

Skin disease, affecting 25-35% of patients, includes • (Lupus pernio): Red to purple indurated plaques of the nose • midfacial papules • annular plaques or nodules on the trunk and extremities. • predilection for scars. • Erythema nodosum is the most common manifestation.

6- Rheumatic diseasePsoriatic Arthritis: (PsA)

• Affects 5-10% of patients with psoriasis. • Asymmetric fusiform swelling of the distal interphalangeal

joints (sausage digits) in 70%.

Lupus Erythematosus: DLE, SLE & SCLE

(DLE) usually localized to the head or neck, is characterized by atrophic, scarring plaques on sun-exposed areas.

• 5% of patients develop SLE.

SLEcutaneous manifestations include • Malar erythema (The butterfly rash): is the

most common expression of SLE.• Photosensitivity• Oral ulcers• Discoid plaques • Bullae • Purpura • Calcinosis cutis • alopecia.

systemic or generalized Scleroderma• Are of 2 forms:1- CREST syndrome: (calcinosis, Raynaud's phenomenon,

esophageal dysmotility, sclerodactyly, telangiectasias). - has a better prognosis

2- Progressive systemic sclerosis.

Dermatomyositis• Symmetric proximal muscle weakness (myositis); • photosensitivity; - Heliotrope: periorbital edema with a violaceous

hue. - Gottron's papules: papules and plaques on the

hands, elbows, and knees and • Telangiectatic plaques with atrophy and

hypopigmentation (poikiloderma) on the face, neck, trunk, and extremities;

• Nail abnormalities (periungual telangiectases and cuticular hypertrophy).

• In adults: Dermatomyositis has a strong association with neoplasm of the breast, GIT, or lung.

7- Gastrointestinal disease

• Dermatitis Herpetiformis (DH)• Acrodermatitis Enteropathica (ACE)• Necrolytic Migratory Erythema (glucagonoma syndrome)

• Lichen planus (LP)• Hereditary Hemorrhagic Telangiectasia (HHT)• Peutz-Jeghers Syndrome• Pyoderma Gangrenosum

Dermatitis Herpetiformis (DH)

is a chronic, intensely pruritic blistering disease • Most patients have an asymptomatic gluten-

sensitive enteropathy • less commonly thyroid disease.

Acrodermatitis Enteropathica (ACE)

• Is an inherited or acquired condition due to zinc deficiency. • Acral and periorificial: pustules, bullae and scaling.• Most patients have diarrhea.• Treatment is zinc supplementation.

Necrolytic Migratory Erythema(glucagonoma syndrome)

• is rare, characterized by erythematous, scaly plaques on Acral, Periorificial or Intertriginous areas + hyperglycemia, diarrhea, weight loss, and atrophic glossitis.• Is in association with an islet cell tumor of the pancreas. • Treatment is rmoval of the tumor.

Lichen planus• violaceous, flat, polygonal papules on the flexor aspects of the

wrists, trunk, medial thighs, genitalia, and oral mucosa. • May occur with: - Primary biliary cirrhosis - Hepatitis B virus immunization or - Gold therapy - In hepatitis C patients: Oral erosive lichen planus.

Hereditary Hemorrhagic Telangiectasia• is an autosomal dominant disorder • characterized by numerous telangiectases on the skin and

oral mucosa. • Recurrent epistaxis is the most common (85 - 90%)

presenting manifestation. • Telangiectases can involve the lungs, liver, brain, eyes, and

GIT hemorrhage can occur at any site. • Pulmonary arteriovenous fistulae and central nervous system

angiomas can also occur.

Peutz-Jeghers Syndrome• lentigines (Lentigo: a brown pigmented spot ) on the skin

(periorbital region, dorsal surfaces of the fingers and toes) and mucosa (lips, buccal mucosa)

• Associated with hamartomas (polyps) of the stomach, small intestine, and colon.

Pyoderma Gangrenosum• painful ulcers with boggy, undermined edges and a border of

gray or purple pigmentation. • The ulcers often follow trauma (pathergy) and begin as

pustules or nodules that ulcerate and extend centrifugally.• legs are the most common site for the ulcers. • 50% of patients have underlying rheumatoid arthritis or

inflammatory bowel disease.

8- Renal diseaseNephrogenic Systemic Fibrosis

(Nephrogenic fibrosing dermopathy)

• Resembles scleroderma. • Thick, indurated plaques on the extremities and the trunk. can be progressive, leading to joint contractures. • In end-stage renal disease• Patients on dialysis.• Acute renal failure or • After kidney transplantation.

9- Endocrine and metabolic disease

Porphyrias: are inherited or acquired disorders of heme biosynthesis. Erythropoietic, Hepatic, or mixed in nature.

Porphyria cutanea tarda (PCT): is hepatic & the most common porphyria,

• Precipitating factors: alcohol ingestion, estrogen administration, certain hepatotoxins (dinitrochlorobenzene, carbon tetrachloride), HIV infection, hemochromatosis, and hepatitis C infection.

• Manifestations of PCT include: - photosensitivity- skin fragility - bullae and erosions on sun-exposed skin (especially dorsal hands), and hypertrichosis. • Treatment includes phlebotomy and antimalarial drugs.

Diabetes Mellitus-Related Skin Conditions

• Cutaneous Manifestations of Diabetes Mellitus: from most to least common.

• 30-50% of diabetic patients develop skin disease. 1- Diabetic dermopathy (shin spots): • Atrophic, hyperpigmented papules and plaques on the

legs

2- Diabetic thick skin: 3- Acanthosis nigricans: Common with obesity and diabetes4- Yellow nails and skin (palms and soles): 5- Acquired perforating disorders 6- Calciphylaxis: is vascular calcification, thrombosis and

skin necrosis: Painful purpuric plaques with ulceration

7- Necrobiosis lipoidica diabeticorum 8- Diabetic bullae