Skin Signs of Systemic Disease

Metabolic Disease

Scurvey – Vitamin C Deficiency

Pathogenesis: Vitamin C acts as a co-factor for prolyl-4-hydroxylase, prolyl-3-hydroxylase, and lysyl hydroxylase, which hydroxylate lysine and proline residues in protocollagen; impaired hydroxylation of lysine and proline leads to defective collagen formation

Clinical Presentation: hair follicle abnormalities (keratotic plugs, vascular proliferation , hemorrhage, hair shaft coiling), gingivitis, poor wound healing

Eruptive Xanthomas – due to dyslipoproteinemias

Pathogenesis: occur in the setting of elevated triglycerides (genetic deficiency of lipoprotein lipase, apoprotein CII, drugs (retinoids), diabetes, pancreatitis, chronic renal failure)

Clinical Presentation: small (2-3mm), yellow-orange to reddish brown papules that appear in crops over the entire body

Hematologic Disorders

Mastocytoses – accumulations of mast cells

Pathogenesis: Mast cells are normal constituents of skin, pulmonary, and GI tracts. An over-accumulation of mast cells leads to skin manifestations while associated histamine and heparin release lead to more serious complications

Clinical Presentation: Mastocytoma (solitary nodule), Urticaria pigmentosa (multiple macules and papules confined to the skin), systemic mastocytosis (internal disease with involvement of lymph nodes, GI tract, Bones, blood, liver, and spleen)

Histamine release Þ abdominal pain, nausea, vomiting, diarrhea, tachycardia

Heparin release Þ bleeding diathesis with hematemesis (vomiting of blood), epistaxis (bleeding from nose), melena (bloody stool), ecchymoses (blood bruise)

Histocytoses X

Pathogenesis: granulomatous proliferation of Langerhans cells (dendritic cells)

Clinical Presentation: involves skin, bones, lungs, and nervous system. 3 distinct entities define the spectrum from worse to better: Letter-Siwe Disease, Hand-Schueller-Christian Disease, eosinophillic granulomatosis.

Coagulation Defects

Purpura: hemorrhage in the skin can be indicative of underlying defects in coagulation cascade, platelet function or #

Thrombocytopenia: low platelets in the blood can be caused by drug sensitivity, autoimmune disease, chemo, etc.

GI Disorders

Sweet’s Syndrome

Pathogenesis: hypersensitivity. Associated with acute myelogenous leukemia, and IBD (ulcerative colitis> Crohn’s)

Clinical Presentation: large, rapidly extending, tender, erythematous plaques typically on the face, neck, and extremities

associated elements of syndrome include fever and leukocytosis

Pyoderma Gangrenosum

Pathogenesis: Associated with ulcerative colitis and other GI problems (polyposis, Crohn’s, gastric ulcers)

Clinical Presentation: rapid appearance of violaceous, boggy, painful ulcers on the legs

Vascular and Pulmonary Disorders

Osler-Weber-Rendu disease (Hereditary Hemorrhagic Telangiectasia)

Pathogenesis: Systemic weakness of vascular walls, endothelial discontinuity and degeneration

Clinical Presentation: tufts of dilated capillaries on the mucous membranes and skin

associated manifestations include epistaxis, melena, splenomegaly, pulmonary and CNS malformations

Atopic dermatitis

Pathogenesis: Type I (anaphylactic) and Type II (cell-mediated) hypersensitivity reactions

Clinical Presentation: Atopic March Þ describes the transition from atopic dermatitis to asthma to hay fever over time

Endocrine Disorders

Pretibial Myxedema – a sign of hypothyroidism

Pathogenesis: Hypothyroidism due to therapy for hyperthyroidism or Hashimoto’s thyroiditis

Cutaneous infiltration is caused by deposition of mucopolysaccharides

Clinical Presentation: bilateral round or oval plaques on lower shins which do not pit on pressure

Also see systemic manifestations of thyroid disease (mental and physical sluggishness, weight gain, asthenia, anemia, etc.)

Calciphylaxis (Parathyroid) – calcifying panniculitis of renal failure

Pathogenesis: Hypercalcemic crisis from renal failure results in the deposition of calcium crystals in the vasculature of the sub-cutaneous fat

Calcium-phosphorus levels can be elevated from non-renal causes as well

Clinical Presentation: Sub-cutaneous nodules and plaques, ecchymoses, epidermal necrosis. 2/3 of cases usually fatal.

Autoimmune Disorders

Lupus Erythematosis

Pathogenesis: Autoimmune disease with potential manifestations in virtually ever organ system.

Clinical Presentation: Erythematosis is frequently used to establish diagnosis

Eleven criteria exist to diagnose, of which four are dermatological: malar erythema, discoid lesions, photosensitivity, oral ulcers.

Cancer

Paraneoplastic Pemphigus

Pathogenesis: autoimmune blistering disease associated with lymphoid neoplasms.

Clinical Presentation: Clinical syndromes of severe mucocutaneous blisters, erosions of pulmonary and GI epithelia

Over 99% of patients have had a lymphoid neoplasm or other malignancy diagnosed

Peutz-Jehgers Syndrome

Pathogenesis: Autosomal dominant disorder characterized by melanin pigmentation of the lips and oral mucosa and benign polyposis of the small intestine.

Clinical Presentation: macules can appear on hands, feet, face, and genital mucosa. Elevated risk of non-GI cancer.

Necrolytic Migratory Erythema – skin eruption of glucagonoma syndrome.

Pathogenesis: glucagon-secreting tumors of pancreatic islet cells

Clincial Presentation: erythematous-brown patches and plaques with flaccid bullae, erosions, and exudative, crusted plaques

Characterized by weight loss, glucose intolerance, anemia, glossitis, hypoaminoacidemia, hypocholesterolemia.

Infectious Diseases

Meningococcemia

Pathogenesis: Neisseria meningitis.

Clincial Presentation: Typical skin findings are petechial

Severe infections: bullous hemorrhagic patches with central necrosis

Systemic signsÞ fever, obtundation, headache, vomiting, stupor, hypertension, neurological

Staphylococcal Scalded Skin Syndrome

Pathogenesis: exfoliation (toxin) elaborated by Staphylococcus areus (Group 2)

Clinical Presentation: most common in young children

Initial focus of infection is typically in the pharynx, nose, ear, or conjunctivae and is released systemically causing skin disease at distant sites.

Other

Acanthosis Nigricans

Pathogenesis: hyperpigmented papillary hypertrophy in a symmetric distribution. Associated with obesity, insulin-resistant states, and endocrinopathy.

Clinical Presentation: "velvety" appearance due to hyperplasia commonly seen in flexor areas of the skin (neck, axillae, groin area, medial thighs, knees, elbows, umbilicus, and anus.

Malignant acanthosis nigricans is associated with adenocarcinomas of the GI tract, lung, and breast

Familial acanthosis nigricans – presents at birth and is accentuated at puberty. Not associated with malignancy. Autosomal dominant inheritance