Cutaneous Manifestations of Systemic Disease

CUTANEOUS MANIFESTATIONS OF SYSTEMIC DISEASE Kathleen Haycraft, DNP, FNP/PNP-BC, DCNP, FAANP, AANP BOD, REGION 7 Objectives • Identify cutaneous manifestations related to /endocrine dysfunction.

• Identify cutaneous manifestations related to renal failure.

• Identify cutaneous manifestations related to gastrointestinal..

• Identify cutaneous manifestations related to internal malignancies. Conflicts of Interest:

■ Celgene ■ Lilly ■ Pfizer ■ AbbVie ■ Valeant ■ Novartis ■ Sanofi/Aventis/Regeneron ■ None will influence the discussion today. Cutaneous Manifestations R/T Endocrine ACA© kathleen Haycraft Acanthosis Nigricans

■ Concern if sudden: – Growth Hormone – Contraception – Malignancy

■ Pearl: Signs of malignancy include: Rapid, pruritic, and extensive acanthosis nigricans in a patient of normal or low BMI Granuloma Annulare

■ Granuloma annulare (GA) is common, self limited, dermatosis of the dermis and subcutaneous tissue. ■ May be local lesions or disseminated ■ May last years or decade ■ Interesting new treatment Augmentin (amoxicillin and clavulanate) 875 bid two weeks. Concerns

■ Associated with DM and thyroid autoimmune disease Diabetes Necrobiosis Lipoidica

© susan Voss Lichen Planus ■ Self-limiting pruritic inflammatory condition ■ Abnormal immune reaction provoked by a viral infection. ■ Strong association with Hepatitis C virus ■ Prognosis is good with the majority of cases resolving within 18 months. ■ The 5 P’s Pruritic, Planar, Polyangular, Purple Papules ■ Wickham’s Striae ■ 2mm-1cm ■ Triggered by Hep B, C, Flu vaccine, Nsaids Lichen Planus

■ Aspartame ■ Graft Vs Host ■ Primary Biliary Cirrhosis ■ May be beta blockers, plaquenyl, thiazide diuretics, furosemide, spironolactone, metformin penicillin, NSAIDs, Hep B, C disease, Flu vaccine Concerns

■ Hepatitis C ■ Hepatitis B ■ LFTs ■ Low but existent risk for DM Xanthelesma

Xanthomas develop from a deposition of cholesterol rich materials. Yellowish in color due to the yellow color of cholesterol. They are common Usually associated with hyperlipidemia. They can occur anywhere on the body and when a xanthoma occurs near the eyelids it is referred to as a xanthelesma. The lesion is soft and usually has sharp demarcations.

Concern: Monitor lipids…less necessary if Xanthelsma. Screen for family history of cardiovascular disease Cutaneous Manifestations Renal Perforating Dermatosis

• Umbilicated dome-shape papules on the arms and legs • Papules hyperkeratotic, ranging in size from 2 to 10mm • Varying degrees of pruritus • Tends to be distributed on trauma-prone areas and often can be reproduced by scratching. Concerns

■ Renal Failure ■ Diabetes Mellitus ■ Refer to Dermatology Calciphylaxis

• Rare systemic Rare syndrome involving vascular calcification and skin necrosis. • Seen with chronic renal failure with dialysis. • Accumulation of calcium deposits in the tunica media of the walls of small arterial vessels is responsible for the presentation of calciphylaxis. Concerns

• High mortality rate of 60-80%. The one year and five year survival rates have been reported at 45% and 35% ,respectively. • The most common cause of death is usually secondary sepsis • REFER TO DERM ASAP Cutaneous GI Seborrheic Keratosis

kathleen haycraft Seborrheic Keratosis

■ The most common cutaneous neoplasm. ■ Correlated with senescence and genetics. ■ Increase after age 40. ■ Associated with failure of keratinocyte repressor gene (FGFR3 and P13K genes). ■ Common sites face, chest, back, and friction sites. Concern:

■ Pigmented SK can mimic melanoma ■ If suddenly occur screen for genitourinary and gastrointestinal malignancy ■ If concerned may refer to dermatology Porphyria Cutanea Tarda

Kathleen haycraft Porphyria Cutanea Tarda ■ Disorder of the heme pathway which causes buildup of porphyrins which are activated by UV light ■ Genetic predisposition that has trigger of alcohol abuse, oral contraceptives, viral illnesses eg HIV and Hep C ■ Fragile skin with vesicles and bullae of sun exposed areas, classically pull hands out of pants and blisters open. ■ Facial hypertrichosis ■ REFER TO DERMATOLOGY Concerns

■ Strong link to hepatitis C ■ May develop hepatocellular carcinoma ■ Modest risk HIV ■ Disease treatment will eliminate PCT Palmar Erythema

■ May be a normal variant ■ Look for alcohol abuse ■ Look for underlying liver disease Dermatitis Herpetiformis

■ Chronic, itchy, burning, blistering rash. ■ Lesions are found symmetrically on the extensor surfaces of the knees, elbows, back, and buttocks. ■ Seen with Celiac Disease Concerns

■ Related to Celiac Disease Cutaneous manifestations related to internal malignancies Muir Torre Syndrome

■ Cutaneous sebaceous adenoma or carcinoma and Keratocanthoma with visceral malignancy GU, GI, small intestinal, some thyroid ■ Lynch syndrome ■ Mismatch repair gene

■ Isotretinoin and interferon have been used to reduce risk Concern

■ REFER TO DERMATOLOGY AND INTERNIST FAMILIAR WITH DISEASE for appropriate screening Puetz-Jehgers Syndrome

©kathleen haycraft Puetz-Jeghers Syndrome

■ Autosomal dominant inherited with hyperpigmentation and polyps ■ Early marked freckling in unusual places eg. Lips, soles of feet and palms. They are blue gray Concerns

■ Small intestine malignancy ■ Refer to Dermatology GI and Oncology Concerns

■ Nanoparticles may be carcinogenic black and red ink are worse ■ Tattoo removal may increase spread ■ Infections esp. Hep C as well as unusual bacteria ■ Allergic Reactions Dermatomyositis

© kathleen haycraft Dermatomyositis ■ Rare autoimmune disease that can affect skin, joints, muscles and many organs ■ Muscle weakness ■ Scaly or psoriaform plaques on forehead and scalp ■ Gottron papules, violaceous hues like violet eyeshadow ■ Pigmentary changes and telangectasias follows shawl sign on sun exposed areas Concerns ■ Myopathies ■ Esophageal involvement ■ Cardiac arrhythmias including conduction abnormalities ■ 10% have interstitial lung disease ■ Esophageal involvement ■ Dependent upon genetic type determines risk for cancer types, always screen for ovarian ■ Cancer risk in first five years with highest in first year. ■ Refer to dermatology also consider rheumatology Bullous Pemphigoid

© kathleen haycraft Bullous Pemphigoid ■ Disease is a tense blistering disease that is bellow the epidermis and is a chronic inflammatory illness that persists for months or years It can have remissions and exacerbations. It can be fatal. ■ Blisters are firm and antibodies attack the area below the epidermis ■ BP 230 and 180 are circulating antibodies that target the hemidesmosome and can be measured for disease severity ■ May be triggered by medications eg diuretics, captopril, antibiotics and neuroleptic agents Pemphigus Vulgaris

■ Autoimmune blistering disease where the antibodies target the epithelial cell and mucous membrane ■ Blisters are soft ■ No known cause is linked to some medications and may be linked to cancers. Concerns: ■ Treatments side effects of immune suppression and ulcers. ■ Dermatologic emergency as affects many mucous membranes in body Sepsis, Treatments put patients at risk for ulcers, immune suppression ■ High risk of sepsis ■ Involves the mucosa in 25% ■ HPN, MI, DM. thromboembolism, neurologic disorders and cancer risks are elevated ■ Optical lesions can result in blindness ■ Cancer development secondary to immune suppression ■ Refer to dermatology Pruritus/Chronic Lichen Simplex

■ Drugs associated with pruritus: ■ Nsaids, steroids, testosterone, opiates, allopurinol, antidepressants, ED drugs, Statins, tamoxifen, antibiotics, ACE, ARB, Beta blocker, Calcium channel blocker, neuroleptics, heparin, amiodarone, biguanides, sulfonylurea derivative diabetic agents Concerns ■ If pruritus has been treated for a reasonable time with cool creams, low potency steroid creams, four time dose antihistamines, negative immuno-cap testing, negative patch testing, gabapentin DO A WORK UP ■ Work up; ■ CMP, TSH, HIV, CBC, Sed, SPEP, CXR, ■ Consider psych referral and further malignancy work up Sweet Syndrome Sweet’s Syndrome ■ Painful violaceous juicy plaque often on back of hand ■ May have a nipple like look ■ May have dusky papules and plaques there may be vesicles and bulla ■ Believed to be a hypersensitivity reaction to drugs or disease ■ Frequently have had a preceding infectious disease that is respiratory Concerns ■ Previous trigger eg. Infection or meds eg., isotretinoin, oral contraceptives, sulfa, furosemide, cyclins, quinolones and cyclins ■ Risks include: – Pyoderma granulosum – Bullous disease – Genitourinary cancer – Hematologic malignancy – REFER TO DERMATOLOGY Systemic Disease with common cutaneous disorders Acne

kathleen haycraft Concerns:

■ The issue of depression, inflammatory bowel disease is likely a comorbid of nodular cystic acne and not due to isotretinoin or doxycycline ■ Screen for GI and depression/suicide Rosacea

■ Genetic link to increase central vasculature of face ■ Initial face is erythrotelengectasia, papular-pustular, granulomatous, ocular rosacea can occur at any point Concern

■ More than double risk of Parkinsons, DM, Celiac, MS, Rheumatoid Arthritis and atherosclerosis ■ Screen for both and refer if concern Photosensitivity

© kathleen haycraft Photosensitivity/polymorphous light eruption ■ Exposure to sun results in sunburn like reaction, more edematous and itchy to painful ■ MED relationship: quinolones, sulfa, furosemide, HCTZ, isotretinoin, antifungals, NSAIDS, phenothiazines, cyclins ■ Polymorphous light eruption usually idiopathic exposure occurs on extensor surfaces and face. A significant proportion of individuals with photosensitivity develop Lupus ■ Screen for arthralgias, ANA with titer annually. Refer if either is significant Dermatofibroma

© Kathleen Haycraft Appearance ■ Asymptomatic but occasionally pruritic or tender. ■ Small, firm, exophytic papule on the lower extremities of adults. ■ The color may be flesh or have tan or brown pigmentation. ■ Hypertrophy of the overlying epidermis may exist. ■ Dermatofibromas characteristically have a dimple sign (Fitzpatrick sign) that occurs when placing lateral pressure with the thumb and forefinger. Dermatofibrosis

■ Concerns: ■ Multiple dermatofibromas (greater than 6) are associated with an altered immune state. The most common is systemic lupus but other disorders include: myasthenia, AIDS, and malignancies. – Even though benign, overlying epidermis has increase risk for BCC..rapid growth is a clue Psoriasis

■ Autoimmune disease that affects many cytokinines that cause hyperkeratinization and angiogenesis ■ Pathways include IL 12, 17, 23, TNF alpha Concerns Medications can trigger: Beta blocker, Lithium, antimalarials Severe stress, bacterial and viral infections Reduces 5 years life span Comorbidities: ■ Psoriatic arthritis ■ CVD, ■ HPN ■ Hyperlipidemia ■ Abdominal aortic aneurysm ■ Stroke ■ Fractures ■ Hypertension Concerns: ■ Obesity ■ Diabetes ■ Depression ■ Malignancy ■ Insomnia ■ Anxiety ■ PEARL Nictotine stimulates the TNF alpha pathway ■ If psoa, severe disease, genitalia, scalp, palmar plantar REFER TO DERMATOLOGY ■ The new world of biosimilars Sebaceous Cyst with SCC

Rapid growth of cyst, painful, expresses white material

■ Look for cancer in rapidly expanding lesion Just a pearl for a pearl’s sake

■ Primary presentation of Zika is itchy papular or macular rash…NO FEVER ■ Powasa virus in ticks is scary Good evening And Good Night References:

■ Bolognia, Jean L., Jorizzo, Josep L., & Shaffer, Julie V. (2012). Dermatology: 2-Volume Set: Expert Consult Premium Edition (3rd ed). Philadelphia, PA: Saunders. ■ DermNet NZ: the dermatology resource. (2016). Retrieved from http://www.dermnetnz.org/ ■ Habif, Thomas B. (2015). Clinical Dermatology (5th ed.). Philadelphia, PA: Mosby. ■ Medscape Reference: Drugs, Diseases, and Procedures. (2016). Retrieved from http://reference.medscape.com/ ■ James, William D., Berge, Timothy, & Elston, D. (2015). Andrews' Diseases of the Skin, 11th Edition (11th ed.). Philadelphia, PA: Saunders. ■ Cutis Journal Years 2016-2017 ■ Bobonich & Nolen (2015). Dermatology for Advance Practice Clinicians. Philadelphia, PA; Wolthers Kluwer Thank you.

■ Kathleen Haycraft, DNP, FNP/PNP-BC, DCNP, FAANP ■ 300 Lovers Leap Dr Hannibal, MO 63401 [email protected] 5737952808