Skin manifestations of internal diseasea

Skin Manifestations of Internal Diseases : 

Skin Manifestations of Internal Diseases Chair Person: Dr Vijaya Laxmi Presenter : Dr Ramakrishna Junior resident General Medicine Nizam’s Institute of Medical Sciences hyderabad

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Dermatologic complaints are a common reason for presentation to a general practitioner. In such cases, one needs to determine if the complaint may be a manifestation of a more serious underlying systemic disease. Disorders of the every organ system may cause skin symptoms and signs, some of which are due to treatment of these conditions. Introduction

SKIN MANIFESTATIONS OF INTERNAL DISEASES : 

SKIN MANIFESTATIONS OF INTERNAL DISEASES Cutaneous manifestations of Diabetes Mellitus Skin and Thyroid Cutaneous aspects of Renal disease Skin & GI tract Hepatic disease and the skin Heart and skin Skin signs of Internal Malignancy Skin changes in Pregnancy

Diabetes Mellitus : 

Diabetes Mellitus Overall prevalence of cutaneous disorders does not differ between type I and type II diabetics Type I patients get more autoimmune-type lesions Type II patients get more cutaneous infections Cutaneous lesions usually appear after the development of DM, but may be the first presenting sign Four major groups of skin findings Skin diseases associated with DM (necrobiosis lipoidica and diabetic bullae) Cutaneous infections Cutaneous manifestions of diabetic complications (neuropathic ulcers) Skin reactions to diabetic treatment

Necrobiosis Lipoidica (Nl) : 

Necrobiosis Lipoidica (Nl) NL appears in 0.3-1.6% of diabetics Appearance Begins as an oval, violaceous patch and expands slowly. Advancing border is red. Central area turns yellowish brown. Central area atrophies and telangiectasia become evident. 13% of cases progress to ulceration

Necrobiosis Lipoidica (NL) : 

Necrobiosis Lipoidica (NL)

Necrobiosis Lipoidica (NL) : 

Necrobiosis Lipoidica (NL)

Granuloma Annulare (GA) : 

Granuloma Annulare (GA) Appearance Ring of small, firm, flesh-colored or red papules If localized, most frequently found on lateral and dorsal surfaces of hands and feet Disease begins with an asymptomatic, flesh-colored papule that undergoes central involution Over months, a ring of papules grows Can spontaneously regress without scarring Histology Focal degeneration of collagen in the upper and mid-dermis, palisaded histiocytes around collagen bundles, and abundant dermal mucin

Granuloma Annulare (GA) : 

Granuloma Annulare (GA)

Granuloma Annulare (GA) : 

Granuloma Annulare (GA)

Diabetic Bullae : 

Diabetic Bullae Two types have been described More frequent, non-scarring lesions with a histologic intraepidermal split without acantholysis Less common, occasionally hemorrhagic bullae that heal with scarring, slight atrophy, and have a histologic subepidermal split Appearance Painless bullae on non-inflamed base that appear suddenly Most common on the dorsa and sides of lower legs and feet, sometimes with similar lesions on the hands and forearms Bullae contain clear, sterile fluid

Diabetic Bullae : 

Diabetic Bullae

Acanthosis Nigricans : 

Acanthosis Nigricans Seen in situations of insulin resistance Besides in DM, also seen in the following: Carcinomas, especially of the stomach Secondary to meds (nicotinic acid, estrogen, or corticosteroids) Pineal tumors Other endocrine syndromes (PCOS, acromegaly, Cushing’s disease, hypothyroidism) Obesity

Acanthosis Nigricans : 

Acanthosis Nigricans Appearance Hyperpigmented, velvety plaques in body folds, mostly axillae and neck Can also present on groin, umbilicus, areolae, submammary areas, and on the hands (tripe hands)

Acanthosis Nigricans : 

Acanthosis Nigricans

Skin Infections in DM : 

Skin Infections in DM Fungal infections- most common Candida Candidal paronychia Inframammary candida Genital candida Psedudohyphae and spores on KOH prep support dx of Candida Purulent drainage may indicate secondary bacterial infection Because maceration and skin breaks can serve as portals of infection, tinea pedis should be treated aggressively in diabetics

Candidiasis in Diabetics : 

Candidiasis in Diabetics Initial pustules on erythematous base that become eroded and confluent

Candidiasis in Diabetics : 

Candidiasis in Diabetics KOH prep showing pseudohyphae and budding yeast forms

Skin Infections in DM : 

Skin Infections in DM Bacterial Infections- can be more severe and widespread in diabetics Malignant otitis externa Pseudomonas aeruginosa Can progress to chondritis, osteomyelitis, and bacterial meningitis

Skin Infections in DM : 

Skin Infections in DM Bacterial infections in DM Erythrasma Reddish tan scaling patches of the upper inner thighs, axillae, toe web spaces, and inframammary creases Gram positive Corynebacterium minutissimum Identified with Wood’s light coral fluorescence

Erythrasma in Diabetics : 

Erythrasma in Diabetics Reddish tan scaling patches of the upper inner thighs, axillae, toe web spaces, and inframammary creases

Cutaneous Manifestations of Diabetic Complications: Foot Ulcers : 

Cutaneous Manifestations of Diabetic Complications: Foot Ulcers Causes for ulcer formation: Peripheral neuropathy (60-70%) Treatment: aggressive debridement and offloading or with a contact cast Vascular disease (15-20%) Treatment: surgical re-vascularization Combination of peripheral neuropathy and vascular disease (15-20%)

Cutaneous Reactions to Diabetic Treatment : 

Cutaneous Reactions to Diabetic Treatment Insulin Allergy may be local or systemic and usually occurs within the first month of therapy Erythematous or urticarial pruritic nodules at the site of injection Lipoatrophy can also occur Circumscribed depressed areas of skin at the insulin injection site 6-24 months after starting insulin More common in women and children Lipohypertrophy can also occur Soft dermal nodules that resemble lipomas at sites of frequent injection

Cutaneous Reactions to Diabetic Treatment: Lipoatrophy : 

Cutaneous Reactions to Diabetic Treatment: Lipoatrophy

Skin And Thyroid: : 

Skin And Thyroid: Pretibial myxedema: Most commonly associated with hyperthyroidism caused by Graves disease. Appear as shiny waxy indurated plaques with prominence of the follicular orifices peau d' orange appearance. Sometimes such lesions appear in other areas as well . It is a cutaneous mucinosis. Generalized myxedema: Most characteristic of hypothyroidism. The entire skin is pale, dry, waxy with a boggy non-pitting edema

Pretibial Myxedema in Graves’ Disease : 

Pretibial Myxedema in Graves’ Disease

Myxedema in Hypothyroidism : 

Myxedema in Hypothyroidism

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Epidermal changes: Dry skin, with scaling in hypothyroidism decreased sebum and eccrine sweat. Moist warm skin in hyperthyroidism ( metabolism). Normal sebum secretion, and eccrine sweat production. Hair: Hypothyroidism: Decreased hair density on scalp and lateral eyebrows. Vitiligo and alopecia areata: May be associated with autoimmune thyroid states.

Cutaneous Aspects Of Renal Disease : 

Cutaneous Aspects Of Renal Disease A variety of inherited and acquired disorders with specific/characteristic renal and cutaneous manifestations exist. This includes diseases in which the same basic process leads to clinical manifestations in both kidney and skin E.g. SLE with deposition of immunoglobulins; amyloidosis with deposition of amyloid. Or the renal and skin involvements are unrelated histologically but still represent different expressions of the same multisystem disease. E.g. tuberous sclerosis, nail patella syndrome , scleroderma and others.

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Nonspecific skin changes that accompany chronic renal disease (namely uremia): Hyperpigmentation: Accentuated on sun-exposed areas ( ­ b - MSH, retained carotene, anemia).   Pruritus: Nature poorly understood - it is hypothesized that the accumulation of metabolites normally cleared by the kidneys as well as dryness contributes to the itching.   Xerosis: excessive dryness. Acquired perforating disorder.

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Uremic frost: terminal finding among patients with severe renal failure numerous white - tan granules, most prominent on the nose, beard area and neck - represent crystallization of urea in sweat. Subepidermal bullous dermatosis Cutaneous calcification: uncommon may be seen in patients with overt hyperparathyroidism may appear as papules/ nodules - may ulcerate and discharge a chalky material. Half and half nail: Proximal white band and distal red-brown band. Xerostomia and stomatitis.

Skin & GI tract: : 

Skin & GI tract: Vascular abnormalities: Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu Disease): Autosomal dominant involves the skin, mucous membranes and numerous internal organs. Multiple small ectatic, vascular lesions are present on face, lips, tongue, nose, hands, chest, feet (to be differentiated from CREST). Epistaxis is the most common form of bleeding. n the GI tract AV malformations, aneurysms may be present as well.   Blue Rubber Bleb Nevus Syndrome: Skin and GI hemangiomas Autosomal dominant or sporadic. Skin lesions few mm to l0 cm vascular papules / nodules and tumors

Osler-Weber-Rendu Disease : 

Osler-Weber-Rendu Disease

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Inherited defects of connective tissue: Pseudo Xanthoma Elasticum: Genetic disorder characterized by alteration of elastic tissue throughout the body. It is characterized by skin lesions, retinal changes, vascular calcifications and GI bleeding. Skin lesions consist of confluent yellowish papules, which form plaques, usually on the neck and axillary areas. Ehlers - Danloss syndrome: 10 different types. (AD, AR or x-linked recessive). Defective connective tissue production. Characteristic findings: hyperextensible and fragile skin, hyperextensible joints, poor wound healing, scarring, easy bruisability

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Ehlers - Danloss syndrome:

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GI Polyposis: Gardner's syndrome: (AD). Colonic adenomatous polyps that may undergo malignant degeneration ( risk). Patients have multiple epidermal cysts on the skin, also osteomas of skin and mandible and desmoid (fibrous) tumors. Peutz - Jeghers syndrome: (AD) hamartomatous polyps throughout GI tract (mainly small intestine). Also risk of GI malignancy, pancreatic and breast carcinomas. Skin: peri-orificial lentiginosis (pigmented lesions). Cowdens syndrome: Hamartomas of skin and mucous membranes. 40% have GI polyps. Have trichilemmomas on skin. Risk of thyroid and breast tumors (usually benign).

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Vasculitis: As part of multisystem involvement; At the level of skin palpable purpuric lesions (usually on lower extremities). e.g.: Henoch-shonlein purpura: leukocytoclastic vasculitis with IgA immune complexes. Affects skin, GI and joints. Tumors: e.g. Kaposi's sarcoma

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Inflammatory Bowel Disease (e.g. ulcerative colitis and Crohn's disease.) Abdominal pain, diarrhea, often associated with blood, pus or mucous. Skin lesions include aphthosis, pyoderma gangrenosum, erythema nodosum and granulomatous skin lesions. Skin and Malabsorption: Ichthyosis -like changes develop (mainly on legs). Brittle hair and nails. Generalized hyperpigmentation due to melanin ( e.g. Addison's disease). May develop stomatitis /glossitis, and dermatitic, psoriasiform lesions due to deficiency in zinc (acrodermatitis enteropathica), essential fatty acids, vitamins A,B,C, and K, folic acid, iron and protein deficiency.

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Granulomas Erythema nodosum

Hepatic Disease and the Skin: : 

Hepatic Disease and the Skin: Alteration in skin color: This is the best recognized cutaneous manifestation of hepatic disease. The two main factors that produce this (may act alone or in combination) are bilirubin and melanin.   Jaundice Deposition of bilirubin (or its metabolites) in tissue (skin, sclera and others) . Here, serum bilirubin is usually greater than 2.5 mg/dl - (NL < l.5 mg/dl).   Hyperpigmentation: Most often associated with hemochromatosis and cirrhosis.

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Hemochromatosis characterized by a triad of liver cirrhosis, DM and hyperpigmentation. can be familial, or acquired. leads to increased iron deposition in various organs, resulting in dysfunction. It is melanin that causes the hyperpigmentation rather than the iron itself. Pruritus: Especially with obstructive disease of the biliary tree. Deposition of bile salts in the skin, is suspected to be the cause. Cutaneous vascular changes: Spider nevi, "liver palms" or palmar erythema. These are believed to be secondary to estrogen levels. Nail changes: Leukonychia (white nails), white bands, koilonychia (spoon nails).

Heart And Skin: : 

Heart And Skin: Subacute bacterial endocarditis (SBE): Vasculitic lesions (Oslers nodes and Janeway's lesions) appearing as purpuric palpable lesions on finger tips, palms and soles. Also splinter hemorrhages (not specific). Petechiae and larger purpuric lesions may be more widespread. Pathogenesis may be immunologic or septic vasculitis

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Figures A-D were obtained from a 17-year-old adolescent with Staphylococcus aureus endocarditis involving the mitral valve. The lesions in Figures A-C were tender and represent Osler's nodes, while the lesion in Figure D was nontender and represents a Janeway lesion

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Familial hyperlipidemia: Increased risk of coronary heart disease. Xanthomatosis may be present in these disorders. Cholesterol emboli: In patients with advanced atherosclerosis of the abdominal aorta, cholesterol crystals may microembolize to the lower extremities. Pulse may remain normal, patients may develop livedo reticularis (reticulated erythematous/vascular pattern) on lower legs, abdomen, with focal cyanosis, crusting and gangrenous changes

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Plane and tuberous xanthomas.

Skin signs of Internal Malignancy: : 

Skin signs of Internal Malignancy: I. Syndromes (some genetically determined with a cutaneous component and an inherent predisposition to internal malignancy): Gardner's syndrome Peutz - Jegher's syndrome Cowden's syndrome Muir-Torre syndrome Neurofibromatosis Mucosal neuroma syndrome Palmar and plantar keratoderma

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Gardner’s syndrome AD(defect ch 5) Epidermoid cysts,fibromas, lipomas,osteomas adenomatous polyps colon Carcinoma

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Peutz-jegher’s syndrome AD Hamartomatous polyps(jejunum) Lips,buccal mucosa,gingiva,.. Ovary,thyroid,cervix CA

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Cowden disease Skin tags,acral keratoses,oral fibroma Breast,thyroid,cervical,colon cancer

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Neurofibromatosis Patient with multiple small cutaneous neurofibromas and a 'café au lait spot Back of an elderly woman with Neurofibromatosis.

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II. Cutaneous markers of exposure to a carcinogen capable of inducing internal malignancy. Arsenic Nicotine staining X-ray damage (radiodermatitis) III. Proliferative, inflammatory, deposition and other skin changes associated with internal malignancy: Pruritus Erythema gyratum repens Sweet's syndrome Hypertrichosis lanuginosa Necrolytic migratory erythema

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Necrolytic migratory erythema : Erythematous macules and papules, often annular or arciform than can progress to erosions

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Clubbing Eruptive seborrheic keratoses Dermatomyositis (adult) Acanthosis nigricans Acquired ichthyosis Flushing Thrombophlebitis Telangiectasia, palmar erythema. Deposition (jaundice, melanosis, hemochromatosis, xanthomas, systemic amyloidosis) Vascular hypersensitivity reaction (e.g. vasculitis, erythema multiforme) IV. Skin Metastasis

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Heliotrope Rash in Dermatomyositis Gottron’s papules

Skin Changes in Pregnancy : 

Skin Changes in Pregnancy Common Alterations of the Skin During pregnancy: Pigmentation: Hyperpigmentation occurs in 90% of pregnant women, more commonly it is localized, involving areas of increased melanocytic density. These areas include areolae, umbilicus, linea alba, genitalia, perineum, axillae, inner thighs. Melanocytic nevi and other pigmented lesions may get darker. Melasma/chloasma (mask of pregnancy) may develop. Cause: estrogen; progesterone and MSH role questionable.

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Vascular changes: The vascular changes result from increased vascular volume and mechanical impairment of blood return leading to venous distension (varicosities arise in 40% of women, lower extremities, rectum, and vulvar areas) these usually regress after delivery. Spider angiomas may appear. Also pyogenic granulomas (epulis), frequently on the gingiva, appearing as red papules/nodules that bleed easily. Hair: Hair loss during first few months following delivery: Telogen effluvium. Striae: Common over lower abdomen and breast.

Dermatoses Usually Associated with Pregnancy: : 

Dermatoses Usually Associated with Pregnancy: Herpes gestationis: Pruritic blistering disease of pregnancy, usually resolves after delivery. Similar to bullous pemphigoid. May affect pregnancy course, and may recur in future pregnancies. Pruritic urticarial papules and plaques of pregnancy (PUPPP) a common gestational dermatosis. Usually starts on abdominal skin (striae). Generally a benign self-limited eruption not affecting fetus.

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Cholestasis of pregnancy (Prurigo Gravidarum): Usually generalized pruritus, may be accompanied by jaundice – onset usually in third trimester. Abnormal liver function tests. Liver biopsy shows dilated bile canaliculi. May be associated with premature labor, low birth weigh and post partumbhemorrhage. Impetigo herpetiformis (pustular psoriasis of pregnancy) the most serious among the dermatoses of pregnancy

Neuro Cutaneous Syndromes : 

Neuro Cutaneous Syndromes Neurofibromatosis Sturge Weber s syndrome Tuberous Sclerosis Von Hippel Lindau Syndrome

Sturge-Weber syndrome : 

Sturge-Weber syndrome Disease that affects the skin and nervous system (neurocutaneous) and is associated with Port Wine Stain, red vascular markings on the face and other parts of the body (shown here on the legs). This is an unusual case, due to the large size of the lesion (extensive involvement). Occasionally seizures or learning disorders are also associated with Sturge-Weber syndrome.

Tuberous Sclerosis : 

Tuberous Sclerosis Skin lesions resulting from TSC include: hypomelanotic macules — patches of skin lighter than the surrounding skin (can be any size or shape or may be the classic "ash-leaf" shape) shagreen patch —a patch of skin that is tough and dimpled like an orange peel periungual or subungual fibromas —fibrous growths that appear around the fingernails and toenails; and facial angiofibromas —tumors of the face

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Cutaneous features of tuberous sclerosis complex include A, hypomelanotic macules and poliosis (in this case, the area of hypopigmentation and poliosis is unusually large; a more typical hypomelanotic macule is evidently inferior to the large lesion); B, facial angiofibromas (adenoma sebaceum); C, the shagreen patch, and D, an ungual fibroma. A B C D

Tuberous Sclerosis : 

Tuberous Sclerosis

Von Hippel – Lindau disease (VHL) : 

Von Hippel – Lindau disease (VHL) It is a rare, autosomal dominant genetic condition in which hemangioblastomas are found in the cerebellum, spinal cord, kidney and retina. These are associated with several pathologies including renal angioma, renal cell carcinoma and phaeochromocytoma.

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Thank You