CUTANEOUS MANIFESTATIONS IN SYSTEMIC DISEASES LECTURER: TRISHA C.

CRISOSTOMO, MD, FPDS

I.

Skin manifestations in the gastrointestinal disease A. Gastrointestinal Malignancy Adult-onset dermatomyositis is associated with underlying malignant disease. Pancreatic, gastric and colorectal cancers are the third most common after bronchogenic and ovarian cancers In two-thirds of patients with acanthosis nigricans and cancer, the tumor is gastric, usually adenocarcinoma of the stomach or bowel. Hypertrichosis lanuginosa is a rare complication of gastrointestinal cancer.

B. Henoch-Schonlein purpura Up to 76% of patients have gastrointestinal involvement, ranging from colicky abdominal pain, nausea and vomiting to bloody diarrhea, intussusception, and pancreatitis.

II. Skin manifestations in the hepatobiliary system A. Chronic Liver Disease Hormone-induced changes of the skin include loss of forearm, axillary and pubic hair in both sexes. Men experience decreased rate of growth of facial hair, pectoral alopecia, and female pubic hair distribution, as well as loss of libido, testicular atrophy and oligospermia. Stria distensae in both men and wome. Telangiectatic changes, mainly on light-exposed skin (dollar paper markings). They fade on pressure with a glass slide and rarely pulsate. In addition to jaundice, a diffuse muddy gray color in patients is due to basal cell melanin.

Spider nevus or spider angioma is the most representative and classic vascular lesion. Most common on the face, neck, and upper part of the chest (i.e., over the region drained by the superior vena cava) Corkscrew sclera vessels (tortuous small arteries that traverse the margins of the ocular sclera)

B. Primary biliary cirrhosis Melanosis is common and may be an early presenting sign. It initially involves exposed areas, but it gradually becomes generalized. Blotchy, circumscribed areas of dirty brown pigmentation Accentuation of normal freckling and areolar pigmentation Localized linear pigmentation may appear in the creases of the fingers and palms. Pigmentation resembling chloasma Guttate hypomelanosis appear on the buttocks, back, thighs and forearms Dermal, subcutaneous and tendon xanthomas are common and can be extensive Pathogenesis: presence of excess melanin with no stainable iron

C. Other skin manifestations of hepatobilary disease Jaundice increased cellular or connective tissue binding of bilirubin and its metabolits in the skin Cholestatic pruritus although retained cutaneous bile acids have been implicated, there is a poor correlation between the plasma bilirubin and the severity of pruritus Nail changes intensely white nails (Terrys nails), splinter haemorrhages, flat or spoon nails Palmar erythema (liver palms)

III. Skin manifestations in the renal system A. Chronic renal failure

Skin of patients are typically dry, often with ichthyosis-like scaling due in part from altered vitamin A metabolism along with the fluid volume shifts of dialysis Skin color is pale from anemia and often exhibits a distinctive gray-yellow hue due to accumulation of carotenoid and nitrogenous pigments (urochromes) in the dermis. Renal pruritus incidence is as high as 90% of patients undergoing hemodialysis. Is thought to be caused by a combination of increased serum histamine, vitamin A and parathyroid hormone; mast cell hyperplasia; peripheral polyneuropathy; and xerosis

Metastatic calcification of the skin results from secondary or tertiary hyperparathyroidism. Abnormally elevated levels of PTH may trigger deposition of crystalline calcium pyrophosphate in the dermis, subcutatneous fat or arterial walls. Occasionally, calcified vessels may thrombose acutely, resulting in calciphylaxis Porphyria cutanea tarda has been described in patients with CRF undergoing hemodialysis - may be due to inadequate clearance of plasma-bound porphyria precursors by urine excretion or hemodialysis; presents as photosensitivity and subepidermal bullae Acquired perforating dermatosis can occur in association with CRF and diabetes mellitus occurs in up to 10% of patients undergoing hemodialysis Nephrogenic fibrosing dermopathy resembles scleromyxedema, presenting with progressively developing erythematous, sclerotic dermal plaques on the arms and legs, with sparing of the head and neck; pruritus is common.

B. Acute renal failure Only two skin changes occure in ARF edema and uremic frost Edema is a particular feature of ARF with nephrotic syndrome Uremic frost results from eccrine deposition of urea crystals on the skin surface of individuals with severe uremia.

IV. Skin manifestations in the cardiovascular system A. Cyanosis An increase in the absolute amount of desaturated (reduced) haemoglobin results in a purple-blue discoloration of the skin. Classified into central and peripheral types, referring to the level of arterial oxygen saturation rather than the anatomic source of cyanosis. Central cyanosis is usually visible on warm areas of the skin such as the tongue, oral mucosae and conjunctivae. Peripheral cyanosis is seen on cooler areas such as the nose, lips, earlobes and fingertips.

B. Erythema Redness of the skin is caused by an increase in the amount of saturated haemoglobin, an increase in the diameter or actual number of skin capillaries, or a combination of these factors. Edema of the face, arms and hands associated with redness and/or cyanosis may indicate obstruction of the superior vena cava due to mediastinal disease.

C. Nail clubbing most commonly occurs in patients with bronchogenic carcinoma, suppurative lung disease, endocarditis and congenital heart disease

V. Skin manifestations in the endocrine system A. Diabetes mellitus 1. Acanthosis nigricans Presents as brown to gray-black papillomatous cutaneous thickening in the flexural areas, including the posterolateral neck, axillae, groin and abdominal folds Distribution is symmetric Affected skin has a dirty, velvety texture The back of the neck is the most consistently and severely affected area

When the palms are involved, the rugated appearance of the palmar surface has been called tripe palms Treatment is generally ineffective and may include calcipotriol, salicylic acid, urea, systemic and topical retinoids. Improvement or resolution does occur with weight loss in some obese patients.

2. Sclerederma diabeticorum Painless, symmetric induration and thickening of the skin on the upper back and neck, spreading to the face, shoulders and anterior torso Skin retains a nonpitting, woody, peau dorange quality Affects 2.5-14% of patients with diabetes and is a disease of longstanding diabetes associated with obesity Treatment is usually unsuccessful, including radiotherapy, low-dose methotrexate, bath psoralen and ultraviolet A light (PUVA), extracorporeal photophoresis, factor XIII, and prostaglandin E1.

3. Eruptive xanthomas 1-4mm reddish-yellow papules on the buttocks and extensor surfaces of the extremities; generally asymptomatic Lesions occur in crops and may coalesce into plaques over time Often with underlying severe hypertriglyceridemia (>1000mg/dl) Eruptive xanthomas respond rapidly to treamtent of hypertriglyceridemia and control of underlying diabetes and usually resolve completely in 6-8 weeks.

4. Diabetic ulcers Callus formation precedes necrosis and breakdown of tissue overy bony prominences of feet, usually on great toe and sole, over first and/or second metacarpophalangeal joints Ulcers are surrounded by a ring of callus and may extend to underlying joint and bone

Standard therapy for neuropathic diabetic ulcers includes debridement, off-loading (often non-weight bearing), moist wound care, and protective dressings.

5. Necrobiosis lipoidica Presents with one to several sharply demarcated yellow-brown plaques on the anterior pretibial region. The lesions have a violaceous, irregular border that may be raised and indurated Initially, NL often presents as red-brown papules and nodules. Over time, the lesions flatten, and a central yellow or orange area becomes atrophic and commonly telangiectasias are visible, taking on the characteristic glazed-porcelain sheen. Aside from the shins, other sites include ankles, calves, thighs, and feet. Although pain and pruritus have been reported, most lesions are asymptomatic. Anesthesia of the plaques does occur. Treatment include topical, intralesional or systemic steroids, topical retinoids and topical PUVA.

6. Diabetic dermopathy Small (<1cm) atrophic, pink to brown scar-like macules on the pretibial areas. Lesions are asymptomatic and clear within 1-2 years with slight residual atrophy or hypopigmentation No treatment necessary.

B.Thyroid disease 1. Hyperthyroidism Likened to infants skin and described as soft, warm and velvety in texture Pruritus may be present Scalp hair is soft and fine, and may be accompanied by a diffuse nonscarring alopecia analogous to telogen effluvium.

Nail changes include soft, shiny and brittle nails with an increased rate of growth Plummers nails concave shape with distal onycholysis; not pathognomonic for hyperthyroidism Pretibial thyroid dermopathy is a classic manifestation of hyperthyroidism and Graves disease. It occurs bilaterally as painless non-pitting nodules and plaques with variable coloring and a waxy, indurated texture.

2. Hypothyroidism Decreased core temperature and increased peripheral vasoconstriction cause the skin to be cool and pale; xerotic Myxedema is the most classic finding. It occurs as a result of dermal accumulation of mucopolysaccharides, namely hyaluronic acid and chondroitin sulphate, and tends to resolve with treatment of the hypothyroidism. Characteristic facial changes include a broadened nose, thickened lips, puffy eyelids, and macroglossia with a smooth and clumsy tongue Skin can be doughy, swollen and waxy but without pitting Hair is coarse, dry and brittle with slowed growth. There can be a loss of eyebrow hair involving the outer third. Nails grow slowly and can be thickened and brittle with longitudinal and transverse striations.

VI. Skin manifestations in rheumatologic and connective tissue disorders A. Rheumatoid arthritis 1. Rheumatoid nodule subcutaneous nodule that occurs in approximately of patients with RA more than 90% of patients have seropositive RA

usual location is over pressure points such as the olecranon, the extensor surface of the forearms and Achilles tendon

2. Bywaters lesions Digital pulp papules associated with nail fold telangiectasias and minute digital ulcerations or petechiae Manifestations of mild vasculitis

B. Lupus erythematosus 1. Acute cutaneous lupus erythematosus Classic butterfly rash or malar rash of SLE Localized ACLE confluent symmetric erythema and edema are centered over the malar eminences and bridges over the nose; nasolabial folds are characteristically spared Generalized ACLE widespread morbilliform or exanthematous eruption often focused over the extensor aspects of the arms and hands and characteristically sparing the knuckles Precipitated or exacerbated by exposure to UV light

2. Subacute cutaneous lupus erythematosus Erythematous macules and/or papules that evolve into hyperkeratotic papulosquamous or annular/polycyclic plaques Characteristically photosensitive and occur in predominantly sunexposed areas (upper back, shoulders, extensor aspects of the arms, V area of the neck, and, less commonly, the face) Typically heal without scarring but can resolve with vitiligo-like leukoderma and telangiectasias

3. Chronic cutaneous lupus erythematosus Classic DLE lesions are the most common form, beginning as redpurple macules, papules, or small plaques and rapidly develop a hyperkeratotic surface Early lesions evolve into sharply demarcated, coin-shaped (discoid) erythematous plaques covered by a prominent, adherent scale that extends into the orifices of dilated hair follicles.

When adherent scale is lifted, keratotic spikes can be seen on the undersurface (carpet tacksign) DLE lesions typically expand with erythema and hyperpigmentation at the periphery, leaving hallmark atrophic central scarring, telangiectasia, and hypopigmentation When present on hair-bearing skin, causes scarring alopecia.

C. Dermatomyositis In 60% of patients, cutaneous lesions and muscle weakness present simultaneously. Onset of cutaneous disease is typically accompanied by pruritus and/or a burning skin sensation Gottron sign and Gottron papules are pathognomonic Periorbital, confluent, macular, violaceous (heliotrope) erythema/edema and grossly visible periungual telangiectasia are highly characteristic

D. Scleroderma (Systemic Sclerosis) Typical presenting features are esophageal reflux and dysmotility and swelling or skin textural changes in the extremities First presentation is typically arthralgia, stiffness and swelling of the extremities. Later, the features of skin sclerosis develop

VII. Skin manifestations in nutritional disease Vitamin A deficiency causes xerotic wrinkled skin covered with fine scales, occasionally accompanied by deep erosions (dermomalacia) Deficiency of vitamin B3 causes pellagra with its triad of diarrhea, dermatitis and dementia Vitamin B12 (cyanocobalamin) deficiency symmetric glove and stocking hyperpigmentation, but a lemon yellow pallor to the skin elsewhere Vitamin C deficiency causes follicular keratoses, hemorrhage and corkscrew hairs Malabsorption of vitamin K leads to cutaneous hemorrhage with ecchymoses and purpura

Folic acid deficiency can present with a diffuse hyperpigmentation, cheilitis and perineal ulceration or dermatitis Iron deficiency presents with angular stomatitis, smooth painful tongue, and fragile/brittle nails, which have longitudinal ridging and lamellation. Marked iron deficiency koilonychia develops. Hair changes include diffuse scalp alopecia with brittle, split hairs Zinc defiency can result from acrodermatitits enterpathica which presents as dermatitis or vesicobullous lesions of the hands, feet, around the mouth and anus, together with progressive alopecia and failure to thrive.