Skin and systemic disease: A framework

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Georgiana Farmer
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1 Skin signs of endocrine disorders Anna Haemel MD Assistant Professor UCSF Dermatology Skin and systemic disease: A framework Crohn s disease Directly related (cutaneous Crohn s) Reactive condition (neutrophilic dermatosis) Associated condition (alopecia areata) Treatment side effect (TNFi induced psoriasis) DM1 Directly related (scleredema adultorum) Reactive condition (N/A) Associated condition (dermatitis herpetiformis) Treatment side effect (insulin injection reaction) 1

Overview Skin manifestations of nonmalignant endocrine d/o incl: Thyroid Hyper Hypo Pancreas Diabetes Androgen excess PCOS Skin manifestations of

2 Overview Skin manifestations of nonmalignant endocrine d/o incl: Thyroid Hyper Hypo Pancreas Diabetes Androgen excess PCOS Skin manifestations of neoplastic endocrine conditions incl: Genetic MEN syndromes Metabolic Glucagonoma Paraneoplastic Dermatomyositis Case 1: Textural changes to legs 2

3 Case 1 Case 1 1 year hx of textural changes to shins> upper extremities Consult question: Does this patient have scleromyxedema? Skin bx forearm dermal mucinosis Labs SPEP/IFE/free light chains neg 3

4 Case 1 Prior hx Graves, incl Graves ophthalmopathy Significant proptosis Significant ocular surface exposure OD>OS No signs of optic nerve compromise Intermittent diplopia that is not bothersome to the patient Graves disease Cutaneous Features Ophthalmopathy (30%) Pretibial myxedema (4%) Acropachy (1%) Stimulation of thyrotropin receptor results in mesenchymal tissue expansion Correction of thyroid level has no effect on skin lesions Transl Pediatr Oct;6(4): Int J Dermatol Aug;54(8):e

5 Thyroid Dermopathy Pretibial Myxedema Accumulation of glycosaminoglycans Bilateral, localized Nonpitting infiltration Nodules and plaques Elephantiasis-like Usually have ophthalmopathy Acropachy is variable Transl Pediatr Oct;6(4): Int J Dermatol Aug;54(8):e280-6 Case 1 Treatment approach Ophtho consult for thyroid associated orbitopathy: Currently inactive Encouraged current attempts to quit smoking Skin directed therapy: Topical/intralesional triamcinolone Compression garments orders (sleeves, gloves, stockings) 5

Case 1 Relative sparing at sites of compression/straps Clubbing Thyroid Acropachy Soft tissue swelling of hands and feet Periosteal reaction of extremity bones Thyroid acropachy is

6 Case 1 Relative sparing at sites of compression/straps Clubbing Thyroid Acropachy Soft tissue swelling of hands and feet Periosteal reaction of extremity bones Thyroid acropachy is associated w severe Graves orbitopathy and need for orbital decompression Transl Pediatr Oct;6(4): Int J Dermatol Aug;54(8):e280-6 Thyroid Dec;13(12):

7 soft tissue swelling onycholysis Thyroid acropachy: periosteal bone formation at the metacarpophalanges and proximal phalanges N Engl J Med Jul 21;375(3):261. 7

Hypothyroidism Myxedema = systemic mucinosis Skin is cold, xerotic, pale Coarse hair Loss of outer third of eyebrow = madarosis Puffy face Broad nose Thick lips and large

8 Hypothyroidism Myxedema = systemic mucinosis Skin is cold, xerotic, pale Coarse hair Loss of outer third of eyebrow = madarosis Puffy face Broad nose Thick lips and large tongue (macroglossia) Drooping eyelids and periorbital swelling MPS deposition Cutis verticis gyrata Carotenemia yellow palms and soles Transl Pediatr Oct;6(4):

9 Hyperthyroidism Skin is warm, moist, and smooth Palmar erythema Facial flushing Hair is thinned, downy Hyperpigmentation Hyperhidrosis Nail changes Plummer nails: concave with distal onycholysis Transl Pediatr Oct;6(4): Int J Dermatol Aug;54(8):e

10 Hyperthyroidism Other Cutaneous Features Vitiligo 7% of patients with Graves disease Increased in patients with Hashimoto's thyroiditis Urticaria Check thyroid antibodies in chronic urticaria Transl Pediatr Oct;6(4):

11 Case 2: Referral for morphea 11

deep dermis Dx: Scleredema adultorum Sclerodermiform

12 Case 2 Skin bx: thickening of the reticular dermis with a slight increase in the amount of interstitial mucin in the deep dermis Dx: Scleredema adultorum Sclerodermiform mucinosis Glycosylation of proteins Transl Pediatr Oct;6(4):

13 Scleredema adultorum Painless non pitting swelling/induration starting on upper back/neck and can spread to upper torso % of pts with DM; more common in men Increased deposition of collagen due to irreversible nonenzymatic glycosylation of collagen/resistance to degradation Very challenging to treat PUVA, MTX, IVIG, other Clin Rev Allergy Immunol Dec;53(3): Skin Signs of diabetes Directly related Scleredema Diabetic cheiroarthropathy Diabetic dermopathy Bullous diabeticorum Acanthosis nigricans Associated conditions Candidiasis Fungal infections Necrobiosis lipoidica Granuloma annulare? Psoriasis 13

14 Diabetic dermopathy Most common cutaneous marker of DM 70% of adults w DM Transl Pediatr Oct;6(4): Bullous diabeticorum Rare but specific (0.05% of pts) Large noninflammatory monolocular bullae on dorsal foot/ankle Image courtesy of Lindy Fox MD Transl Pediatr Oct;6(4):

Acanthosis nigricans assoc w insulin resistance AN is a sign of peripheral insulin resistance Increased in groups with DM commonly (NA, Hispanics, AA s) and in obesity Elevated insulin levels bind to

15 Acanthosis nigricans assoc w insulin resistance AN is a sign of peripheral insulin resistance Increased in groups with DM commonly (NA, Hispanics, AA s) and in obesity Elevated insulin levels bind to Insulin Growth Factor receptors on keratinocytes causing AN Transl Pediatr Oct;6(4): Skin Signs of diabetes Directly related Scleredema Diabetic cheiroarthropathy Diabetic dermopathy Bullous diabeticorum Acanthosis nigricans Associated conditions Candidiasis Dermatophytosis Necrobiosis lipoidica Granuloma annulare? Psoriasis 15

16 16

17 Necrobiosis lipoidica diabeticorum 0.3% to 1.6% of pts w DM BUT 75% of cases of NLD occur in pts who have or will develop DM Case 3: Severe adult female acne 28 YOF Acne in teens, now recurrent again in late 20s Irregular menses, excess hair growth, thinning scalp hair A1c = 5.8% 17

Photo courtesy of Kanade Shinkai MD, PhD PCOS and skin 72-82% of pts w PCOS have cutaneous signs of hyperandrogenism Acne - 61% of pts w PCOS not a reliable marker Hirsutism 53% of pts w PCOS

18 Photo courtesy of Kanade Shinkai MD, PhD PCOS and skin 72-82% of pts w PCOS have cutaneous signs of hyperandrogenism Acne - 61% of pts w PCOS not a reliable marker Hirsutism 53% of pts w PCOS excellent marker Acanthosis nigricans 37% of pts w PCOS excellent marker Hirsutism and AN are both assoc w elevated free testosterone level and increased insulin resistance Schmidt T et al (2016) JAMA Derm, 152:

19 Hirsutism - a specific sign in PCOS Photo courtesy of Kanade Shinkai MD, PhD Photo courtesy of Kanade Shinkai MD, PhD 19

20 Acanthosis nigricans is specific sign in PCOS Photo courtesy of Kanade Shinkai MD, PhD Androgenetic alopecia - not a reliable marker of PCOS Schmidt T et al (2015) JAMA Derm, Dec 23:1-8 20

21 Treatment Weight loss Dietary changes OCPs Metformin as needed for hyperglycemia Spironolactone for hirsutism, acne Dermatology & disorders of androgen excess PCOS (most common) CAH Ovarian tumors Adrenal tumors 21

22 Case 4 22

Necrolytic migratory erythema (assoc w glucagonoma) Glucagonoma syndrome: NME skin findings, incr glucagon levels, diabetes/glucose intolerance NME: Migratory plaques w

23 Necrolytic migratory erythema (assoc w glucagonoma) Glucagonoma syndrome: NME skin findings, incr glucagon levels, diabetes/glucose intolerance NME: Migratory plaques w superficial epidermal necrosis, central flaccid bullae, and crusted erosions Favors flexural areas Skin may respond to somatostatin analog (octreotide) Int J Dermatol Feb

24 Skin manifestations of neoplastic endocrine disorders Metabolic/neuroendocrine Glucagonoma Paraneoplastic Dermatomyositis Genetic MEN syndromes Necrolytic migratory erythema (assoc w glucagonoma) Pathogenesis: metabolic etiology involving excess glucagon, amino acid deficiency, zinc deficiency, and free fatty acid deficiency Skin may impove w IV amino acid supplementation or zinc Clinically appears similar to eruption of acrodermatitis enteropathica Int J Dermatol Feb

25 Skin manifestations of neoplastic endocrine disorders Metabolic/neuroendocrine Glucagonoma Paraneoplastic Dermatomyositis Genetic MEN syndromes 25

Risk is highest in first 2 years, but remains elevated out to 5 years

26 Malignancy in dermatomyositis Most studies have found an increased risk of cancer with DM in up to 30% of patients Ovarian cancer over-represented Risk is highest in first 2 years, but remains elevated out to 5 years Disease may improve with cancer treatment Am J Clin Dermatol Apr;16(2):

Palmar fasciitis - polyarthritis: Assoc w ovarian cancer Clin Exp Dermatol. 2017 Apr;42(3):328-330.

27 Palmar fasciitis - polyarthritis: Assoc w ovarian cancer Clin Exp Dermatol Apr;42(3): Skin manifestations of neoplastic endocrine disorders Metabolic/neuroendocrine Glucagonoma Paraneoplastic Dermatomyositis Genetic MEN syndromes 27

MEN Type I: Wermer Endocrine: Parathyroid hyperplasia, islet cell tumors, pituitary adenomas Skin: Facial angiofibromas, collagenomas, (sometimes) lipomas Semin Oncol. 2016 Jun;43(3):335-40.

28 MEN Type I: Wermer Endocrine: Parathyroid hyperplasia, islet cell tumors, pituitary adenomas Skin: Facial angiofibromas, collagenomas, (sometimes) lipomas Semin Oncol Jun;43(3): Arch Dermatol Jul;146(7):715-8 MEN IIA: Sipple Endocrine: Parathyroid hyperplasia, medullary thyroid carcinoma, pheochromocytoma Skin: Macular and lichen amyloid, notalgia paresthetica Semin Oncol Jun;43(3):

29 MEN IIA and lichen amyloid Clin Endocrinol (Oxf) Aug;59(2): MEN IIB: Multiple mucosal neuromas syndrome Endocrine: Medullary thyroid cancer, pheochromocytoma Skin: Multiple mucosal neuromas, marfanoid habitus, joint laxity Semin Oncol Jun;43(3):

30 Questions? 30

Common Cutaneous Signs of Medical Illnesses

Common Cutaneous Signs of Medical Illnesses DR COLIN THENG MBBS, MMED (FAM. MED), MRCP(UK), FAMS SENIOR CONSULTANT DERMATOLOGIST THE SKIN SPECIALISTS & LASER CLINIC MOUNT ALVERNIA MEDICAL CENTRE D, #07-61