Dermatology from the Inside Out

Dyanne P. Westerberg, DO

8/3/2015

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Dermatological Manifestations of Systemic Disease

Dyanne P. Westerberg, DO. FAAFPAssociate Professor and Founding Chair

Department of Family and Community MedicineCooper Medical School Rowan University

Camden , New Jersey

Goals

Certain skin disorder are frequently associated with internal disease. The skin lesion itself may be insignificant but should prompt the clinician to search for possible internal illness. The goal of this lecture is to review several common skin conditions and their possible associated internal disorders. There are many such cutaneous problems. The purpose of this talk is to review more common pathological problems.

Paraneoplastic Syndromes

• Cutaneous symptom which is a consequence of an internal disease i.e neoplasm

• Broad range of diseases

• Believed to be due to result of biological active hormones, growth factors immunologic complexes induced by or produced by the tumor

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A 42 yo female patient presents with dry, thickened, scaly or flaky skin and she feels it resembles the scales on a fish;

http://dermnetnz.org/dermatitis/img/ichthyosis-s.jpg

Cutaneous lesions and Internal Malignancy

• Ichthyosis: It has been described in association with malignancies, drugs, endocrine and metabolic disease, HIV, infection, and autoimmune conditions.

– Hodgkins

– Lymphoproliferative disorders

– Cancer of the lung, breast and cervix

A 46 yo male presents to the office with a complaint of abrupt appearance of black ovals on this back. They started to appear about 3 months ago and OTC hydrocortisone cream did not help. On exam you see numerous sebrrheic keratosis lesions http://www.51qe.cn/pic/30/12/17/41/b/00701.jpg

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Leser-Trelat

• Abrupt appearance of numerous seborrheic kerratosis

• 3 to 6 months

• Types

• Most are adenocarcenomas of the GI tract

• Others breast, lung, urinary tract, lymph tissue

A 51 yo female presents to the office with a complaint of itchy skin on the nipple of the left breast. It has been present for 3 months and it has not resolved despite a change in soap and use of OTC hydrocortisone cream. Yesterday a bloody discharge started and she believes this is due to the increased scratching. She has not felt a lump.

http://www.oncoprof.net/Generale2000/g01_HistoireGenerale/Images/PagetSein.jpg

Paget’s Disease of the breast

• Breast cancer: Most women have underlying ductal breast cancer

• Appears to be eczema - may be associated with discharge

• It is common for the symptoms to disappear for a while, which may make the patient think incorrectly that the condition has cleared up spontaneously.

• Most women do not visit the doctor because they take Paget's disease to be minor contact dermatitis or eczema

• Should encourage mammogram and biopsy

• Most patients diagnosed with Paget's disease of the nipple are over age 50

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A 10 yo male presents to the office for evaluation of stomach upset. This has been going on for a few days. He is brought in by his mother who states that the father has some type of stomach problem but she has not seen him in years and doesn’t know what it is. Before you start the exam you notice that the child has darkly pigmented spots on the lips and buccal mucosa.

http://drugster.info/img/ail/3127_3150_3.jpg

Peutz- Jegher Syndromeaka Hereditary Intestional Polyposis Syndrome

• Autosomal dominant

• Patches of hyperpigmentation in the mouth and on the hands and feet and may fade by adulthood

• characterized by the development of noncancerous growths called hamartomatous polyps in the gastrointestinal tract (particularly the stomach and intestines) causing abdominal pain and GI bleeding.

• Adenocarcenoma of the stomach, duodenum, pancreas and colon. Also esophagus, ovary, lung, uterus and breast.

• Intussusception in 47% of 222 patients with Peutz-Jegherssyndrome in Japan between 1961-1974

A 16 yo female present to the office as a new patient for a physical exam. During the course of the exam you note an overweight female patient. On her neck you find symetric,hyperpigmented, hyperkeratotic and verrucousplaques. She mother reported that these lesions seem to have gradually erupted over the past few years. Various creams and soaps did not get rid of these lesions.

http://imaging.cmpmedica.com/shared/zone5/0812CFPILEF1.jpg

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Acanthosis nigricansCauses: •Obesity ( majority)

•Insulin resistance

•Excessive corticosteroids

•Drugs i.e Oral contraceptives

•Adenocarcemoma

•In thin individuals: malignancy

Location: axilla most common , also nape of neck, groin, belt line , aerola, dorsum of fingers

Pathogenesis:

•caused by factors that stimulate epidermal keratinocyte and dermal fibroblast proliferation.

• In 2000, the American Diabetes Association established acanthosis nigricans as a formal risk factor for the development of diabetes in children.

• Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am Acad Dermatol. Sep 2007;57(3):502-8

Image 1:http://www.skinsight.com/images/dx/webChild/acanthosisNigricans_22933_lg.jpg

Image 2: http://www.cssd.us/images/diagnoses/endo7.jpg

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Acanthosis nigricans

• I hereditary – benign• II benign –

– associated with endocrine disease usually insulin-resistance state such as polycystic ovarian disease, lipodystrophies, type 2 diabetes mellitus, and several genetic disorders

– about 15% of adults with obesity and Acanthosis Nigricans have an endocrine abnormality e.g Cushing’s Disease

• III pseudo - complication of obesity (rapid weight gain)• IV drug-induced - oral contraceptives, nicotinic acid, corticosteroids,

subcutaneous insulin, testosterone, diethylstilbestrol, triazinate (a folate antagonist with antitumor activity) and topical fusidic acid (Fucidin, used for gram-positive bacterial skin infections)

• V malignant - usually gastric adenocarcinoma, also seen with endocrinologic and lung malignancies, lymphoma, melanoma, sarcomas, and genitourinary tract cancers– Type V seen most often in

• non-obese patients with sudden onset, • severe or rapidly progressive involvement• mucous membrane or prominent palm and sole involvement• no easily discernible cause

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Acanthosis nigricans

• I hereditary – benign• II benign –

– associated with endocrine disease usually insulin-resistance state such as polycystic ovarian disease, lipodystrophies, type 2 diabetes mellitus, and several genetic disorders

– about 15% of adults with obesity and Acanthosis Nigricans have an endocrine abnormality e.g Cushing’s Disease

• III pseudo - complication of obesity (rapid weight gain)• IV drug-induced - oral contraceptives, nicotinic acid, corticosteroids, subcutaneous

insulin, testosterone, diethylstilbestrol, triazinate (a folate antagonist with antitumor activity) and topical fusidic acid (Fucidin, used for gram-positive bacterial skin infections)

• V malignant - usually gastric adenocarcinoma, also seen with endocrinologic and lung malignancies, lymphoma, melanoma, sarcomas, and genitourinary tract

cancers*****

– Type V seen most often in• non-obese patients with sudden onset, • severe or rapidly progressive involvement• mucous membrane or prominent palm and sole involvement• no easily discernible cause

*****

A 32 yo female presents to the office with a lesion on the left anterior fibula. It has gradually gotten worse over the years. On exam you notice slightly raised shiny red-brown patches. The centers are yellowish.

http://t3.gstatic.com/images?q=tbn:ANd9GcSaXLUmj5P2q_rRFsBT86X02mx3MMLfXfv2W620YrITfox16ZoV5Q

Necrobiosis lipoidica

•Unknown origin

•>50% DM

•May appear years prior to the onset of DM

•Commonly in 3rd and 4th decade

•Most commonly females

•Most anterior surfaces of the legs

•Starts as small ovals

•Waxy yellow skin with telangietasia

•eventually the skin atrophies

•ulcers form

•Treatment

•Steroids

•Pentoxifylline

•Aspirin and dipyridamole

•Skin grafting

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Bowen Disease

Bowen’s disease is a very early form of skin cancer that appears as a slow-growing, red and scaly skin patch. In Bowen’s disease, the skin cancer is located only in the epidermis, the uppermost layer of the skin. Rarely, the skin cancer can invade into the dermis and then it is called an invasive squamous cell carcinoma.

Differential

Stasis Dermatitis

• insufficient venous return

• can lead to increased pressure on capillaries in the extremities

• blood collects in the intracellular spaces rather than being drawn back into the circulatory system

: http://t2.gstatic.com/images?q=tbn:ANd9GcReB7FykYvQzkqR7jtssOLLLPMaZyGPY96oRurIxrwPmqJRdB7cSg

Cellulitis

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Granuloma Annulare

•Appearance:

•reddish bumps arranged in a circle or ring.

• Types:

• localized, disseminated, subcutaneous, and perforating.

•Unknown etiology :

•shown to follow trauma, malignancy, viral infections (including human immunodeficiency virus [HIV], Epstein-Barr virus, and herpes zoster), insect bites, and tuberculosis skin tests 12% of patient have DM

•Differential: Tinea Corporus

•Treatment

•None unless bothered by appearance

•Triamcinolone injection, topical steroids etc

http://images.medicinenet.com/images/image_collection/skin/granuloma-annulare.jpg

Diabetes Mellitus

• Candida

• Carotenodermia

• Diabetic Bullae

• Diabetic Dermopathy

• Diabetic Thick Skin

• Erythema

• External Otitis

• Finger Pebbles

• Foot Ulcer

• Acanthosis Nigricans

• Gas Gangrene

• Granuloma Annulaire

• Insulin Lipodystrophy

• Necrobiiosis Lipoidica

• Yellow Nails

• Perforating disorders

• Eruptive Xanthomas

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Myxedema•syndrome of painless nodules that occur over the pretibialareas

•subcutaneous accumulation of mucopolysaccharide-rich material

•Stimulation of fibroblasts

• A complication of Graves Disease: 1-4% but also seen in primary hypothyroidism or Hashimoto's thyroiditis

•Associated with Graves’ophthalmopathy,

http://2.bp.blogspot.com/-WRLc3o-VTfs/TbvtZ-ezbSI/AAAAAAAAABE/sGENUs5uppo/s1600/myxedema.jpg

Xanthomas

•Lipid deposits in the skins and tendons due to elevated serum lipids

http://dermatology.cdlib.org/123/case_presentations/xanthoma/1.jpg

A 54 yo female present s to the office with a complaint of flat yellow lesions aroundher eyes. You note that they

are soft to the touch and have sharp edges.

Types

Type clinical abnormality

Xanthelasma Inner and outer canthus, plane or papular

May not have lipid problem

Eruptive Yellow papules on red baseButt, elbows, knees

High triglycerides, DMType I,II, IV hyperlipidemia

Plane Palms and face, neck, chest Biliary cirrhosis, Type III

Tuberous Nodular on elbows and knees

High triglycerides, Type II and III biliary cirrhosis

Tendinous Nodules on elbow and knees, Achilles tendon , hands and feet

Type II

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Types of Xanthomas

Eruptive XanthomasImage 1

Tuberous XanthomasImage 2

Image 1: http://www.healthcare.uiowa.edu/dermatology/Images%5CClin%5CErupXan-01-low.jpg

Image 2:http://2.bp.blogspot.com/_v2ER6lx2y4w/TRwxzxSOsPI/AAAAAAAAACU/g__C8DdET28/s1600/xanthoma_tuberous.JPG

Types of Xanthoma

Plane XanthosisImage 1

Tendinous XanthomasImage 2

Image 1:http://www.dermnet.org.nz/systemic/img/xanth-palm-s.jpg

Image 2http://3.bp.blogspot.com/_xzqs4DHM8as/TLSpR90RV-I/AAAAAAAAAGo/2KiF6LfV_ng/s320/xanthoma+tendon.jpg

Café- au - lait maculesImage 1

NeurofibromasImage 2

Image 1http://www.hardsweat.com/wp-content/plugins/wp-o-matic/cache/60d73_cafe-au-lait-spot_1.jpg

Image 2http://meded.ucsd.edu/clinicalimg/skin_neurofibroma1.jpg

Malignant degeneration to neurofibromasarcoma or malignant schwannomacan occur

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Neurofibromatosis

• Autosomal Dominant Disorders but commonly due to mutation

• Affects all neural crest cells• Presumptive Diagnosis

– Prepubital: 6 or more café au lait spots > 5 mm diameter– Post puberty: 6 or more café au lait spots > 15 mm diameter

• Types:– neurofibromatosis type 1 (NF1, also called von Recklinghaus

disease), – neurofibromatosis type 2 (NF2), associated with hearing loss – schwannomatosis. Associated with intense pain

Tuberous SclerosisSkin:

Areas of the skin that are white (due to decreased pigment) and have either an ash leaf or confetti appearance

Red patches on the face containing many blood vessels (adenoma sebaceum)

Raised patches of skin with an orange-peel texture (shagreen spots), often on the back

Image 1http://t3.gstatic.com/images?q=tbn:ANd9GcS22v7Y-BxpcxJH6Jmygnpi-CKf3y60vYAsJiTJOz6oAmTIzn8t

Image 2 :http://dermis.net/bilder/CD014/550px/img0075.jpg

Image 3: http://www.uth.tmc.edu/GeneWise/LumpsBumpsSpots/images/slide31.png

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Tuberous sclerosis

• Inherited Disorder - Dominent

• Mutations in two genes, TSC1 and TSC2

• Affects skin, nervous tissue, kidneys and heart

• With proper care, patients do well

• Symptoms:

– Developmental delays

– Mental retardation

– Seizures

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Urticaria•polymorphic, round or irregularly shaped pruritic wheals

•lesions can appear hyperemic in the center with a white halo along the circumference

•Size: varies

•Histamine released from cutaneousmast cells and basophils in response to inciting stimuli

•Lab evaluation of little value

http://www.webmd.com/skin-problems-and-treatments/picture-of-hives-urticaria

Angioedema

•can occur alone or with urticaria

•nonpitting, non-pruritic, well-defined, edematous swelling

• involves subcutaneous tissues (e.g., face, hands, buttocks, genitals), abdominal organs, or the upper airway (i.e., larynx)

Common causes of angioedema and urticaria

• Nonimmunologic causes

– Physical stimuli: exposure to sun, water, or temperature extremes; delayed pressure (e.g., wearing a heavy backpack); vibration

– Direct mast cell degranulation: opiates, vancomycin , aspirin, radiocontrast media, dextran, muscle relaxants, bile salts, NSAIDs, ACE inhibitors

– Foods containing high levels of histamines: strawberries, tomatoes, shrimp, lobster, cheese, spinach, eggplant

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Common causes of angioedema and urticaria

• Immunological Causes

– Type I IgE-mediated

• Foods: tree nuts, legumes, crustacea, mollusks, fish, eggs, milk, soy, wheat

• Organic substances: preservatives, latex, hymenoptera venom

• Medications: penicillin, cephalosporin, aspirin, NSAIDs

• Aeroallergens: dust mites, pollens, molds, animal dander

– Type II cytoxic antibody-mediated: transfusion reaction

– Type III antigen-antibody mediated: serum sickness reaction

– Type IV delayed hypersensitivity: medication, food handling, or exposure to animals

• Autoimmune disease: Hashimoto's disease, systemic lupus erythematosus, vasculitis, hepatitis

• Infection: viral (e.g., cytomegalovirus, Epstein-Barr, hepatitis), parasitic, fungal, or bacterial

What does this have to do with systemic

Disease??

Treatment

• long-acting, nonsedating histamine H1-receptor antagonist

• first-generation H1-receptor antagonist, such as hydroxyzine

• H2-receptor antagonist has shown benefit in the management of urticaria in controlled clinical studies

• Cyproheptadine (periactin)• Doxepin (adapin)• Leukotriene modifiers such as montelukast or

zafirlukast• short-term course of oral glucocorticoids

Strep Pharyngitis

Group A beta hemolytic streptococcus

http://www.webmd.com/cold-and-flu/slideshow-anatomy-of-a-sore-throat

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http://www.goodtoknow.co.uk/health/133316/Scarlet-fever-in-children

Scarlet Fever

– bright red, scarlet rash on their chest and neck, which then spreads to the rest of their body

– rash blanches

– flushed face

– strawberry tongue

– fever and general malaise

Rheumatic Fever – Arthritis

– Carditis

– Subcutaneous nodules

– Sydenham chorea

– Skin rash (erythemamarginatum) -- 5% of patients

• Erythemaous rings

• Non puritic

http://images.rheumatology.org/viewphoto.php?albumId=75683&imageId=2862052

http://www.beltina.org/health-dictionary/erythema-nodosum-symptoms-treatment.html

Erythema Nodosum

– tender red lumps from 1 to 5 centimeters

– most commonly located over the shins

– most common form of panniculitis(inflammation of the subcutaneous fat)

– The peak incidence of EN occurs between 18–36 years of age.

– Resolves 3 to 6 weeks

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• Infections. Streptococcus (most common)– Cat scratch disease– Chlamydia– Coccidioidomycosis– Hepatitis B– Histoplasmosis– Leptospirosis– Mononucleosis (EBV)– Mycobacteria– Mycoplasma– Psittacosis– Syphilis– Tuberculosis– Tularemia– Yersinia

• Pregnancy• Sensitivity to certain

medications, including:– Antibiotics including

amoxicillin and other penicillins

– Sulfonamides– Sulfones– Birth control pills– Progestin

Guttate Psoriasis

Image 2

http://www.webmd.com/skin-problems-and-treatments/psoriasis/slideshow-severe-psoriasis-9

– salmon-pink drops on the skin

– 80% occur after strep infection

– about 2-3 weeks after the infection

– more common in children and adults younger than 30 years

Lyme Disease•a systemic illness resulting from infection with the spirochete Borreliaburgdorferi

•most prevalent in children two to 15 years of age and in adults 30 to 59 years of age

•The onset of clinical manifestations -within 7 to 10 days after a tick bite, with a reported range of one to 36 days.

•Most patients (60 to 80 percent) develop the early, localized form of Lyme disease

•May have associated influenza-like symptoms

http://geology.com/articles/ticks-lyme-disease

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Dermatitis Herpitiformis

•Duhring's Disease

•Chronic Blistering Skin condition

•Extremely itchy

•Itch and burning may appear prior to the onset of the rash

•Associated with Celiac disease

•Will improve with gluten free diet

http://www.primehealthchannel.com/dermatitis-herpetiformis-pictures-symptoms-causes-and-treatment.html

A patient of any age presents to the office with red or purple maculas on the skin that do not blanch on applying pressure.

HENOCK- SCHÖNLEIN PURPURA

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Kawasacki Disease Awareness:http://www.facebook.com/note.php?note_id=85263843435

Petechiae or Purpura

http://www.noblis.org/MissionAreas/nsi/BackgroundonBiologicalWarfare/BiologicalWarfareOrganisms/Pages/Rickettsiae.aspx

Purpura measure 0.3–1 cm (3–10 mm), whereas petechiae measure less than 3 mm, and ecchymoses greater than 1 cm. They can be seen with clotting problems, associated with infections i.e Meningitis, rocky mountain spotted fever and vasculitis i.e Henoch-Scholein Purpura

Sarcoidosis

•systemic disease of unknown cause with noncaseatinggranulomas

•skin involvement occurs in about 20-35% and may be first presentation

•2 forms of cutaneous sarcoidosis

•specific skin lesions contain noncaseating granulomasand may includemaculopapules

•Plaques

•nodules

•Lupus perno: indurated, lumpy, lesions on nose, cheeks, lips, and ears

•scar infiltration

•alopecia

•ulcerative lesions

•hypopigmentation

•nonspecific skin lesions (without noncaseatinggranulomas)

•calcifications

•Prurigo – itchy erruptions of the skin

•Erythema multiforme

•nail clubbing

•Sweet syndrome – fever and red bumps on the arm

http://dermatology.cdlib.org/133/case_reports/pernio/3.jpg

Most characteristic

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Systemic Lupus Erythematosis

•multisystem, autoimmune disorder of connective tissue

•Butterfly rash

•Erythema Multiforme type rash

•Skin lesions may worsen with sun exposure

•Alopecia is also common

•Discoid Lupus is associated only with skin manifestations

http://www.cedars-sinai.edu/Patients/Health-Conditions/Images/351457_Lupus-1.jpg

http://dermatology.cdlib.org/1508/articles/2008102101/1.jpg