Lecture #187: Dermatologic Signs of Systemic Diseases

What is the main purpose of recognizing skin signs of systemic disease?

Skin, hair, and nail findings can provide diagnostic clues to systemic diseases, especially autoimmune connective tissue diseases, GI disorders, liver disease, renal failure, malignancy, cardiovascular disease, and nutritional deficiencies.

How is lupus erythematosus classified by skin involvement?

Lupus erythematosus is classified as acute cutaneous LE, subacute cutaneous LE, and chronic cutaneous LE; acute cutaneous LE is practically always associated with systemic lupus erythematosus and is highly photosensitive.

What are the diagnostic criteria for SLE summarized by “RASH OR PAIN”?

SLE diagnosis requires 4 of 11 criteria: malar rash, discoid rash, arthritis, serositis, hematologic disorder, oral ulcers, renal disease, photosensitivity, ANA positivity, immunologic disorder, and neurologic disorder such as seizures or psychosis.

What is the classic malar rash of SLE?

The malar or butterfly rash is an erythematous plaque-like rash across the cheeks and nasal bridge that classically spares the nasolabial folds.

What are key features of discoid lupus erythematosus?

Discoid lupus causes erythematous papules or plaques with adherent keratotic scale, follicular plugging, atrophic scarring, and may cause scarring alopecia.

What are “carpet tack” spines in discoid lupus?

“Carpet tack” spines are keratotic projections seen on the undersurface of adherent scale in discoid lupus, reflecting follicular plugging.

What antibodies are high yield in SLE?

ANA is positive in more than 95%; anti-dsDNA may indicate kidney and skin disease, anti-Smith is associated with kidney disease, anti-Ro/SS-A is associated with skin and kidney disease plus fetal heart problems, and antiphospholipid antibodies are associated with thrombosis and pregnancy loss.

What drugs are classically associated with drug-induced lupus?

Drug-induced lupus is associated with anti-histone antibodies and is commonly caused by “HIP”: hydralazine, isoniazid, and procainamide.

What is subacute cutaneous lupus erythematosus?

Subacute cutaneous LE presents with annular erythematous rings or papulosquamous psoriasiform lesions; about 50% develop 4 or more SLE criteria, 60–80% have positive ANA, anti-Ro/SS-A is positive in more than 80%, and anti-La/SS-B is positive in 30–50%.

How is lupus evaluated?

Evaluation includes history and physical, CBC, autoantibodies, urinalysis for proteinuria or hematuria, and biopsy of lesional, non-lesional, and non-sun-exposed skin with immunofluorescence/lupus band testing.

How is lupus treated?

Treatment includes sun protection, topical/intralesional/systemic steroids, antimalarials such as hydroxychloroquine, and immunosuppressants when needed.

What is dermatomyositis?

Dermatomyositis is an autoimmune disease targeting skin and muscle, associated with drugs, infections, trauma, vaccination, malignancy, pregnancy, and abnormal antinuclear antibodies such as anti-Jo-1.

What findings support probable dermatomyositis?

Probable dermatomyositis requires a cutaneous finding plus 2 of 4 muscle findings: proximal symmetric muscle weakness, elevated muscle enzymes, abnormal EMG, or abnormal muscle biopsy.

What cutaneous findings are pathognomonic for dermatomyositis?

Heliotrope rash and Gottron’s papules are pathognomonic cutaneous findings of dermatomyositis.

What is a heliotrope rash?

A heliotrope rash is a violaceous or erythematous rash around the eyes/eyelids associated with dermatomyositis.

What are Gottron’s papules?

Gottron’s papules are erythematous to violaceous papules over bony prominences, especially MCP, PIP, DIP joints, elbows, or knees, and are pathognomonic for dermatomyositis.

What other skin findings occur in dermatomyositis?

Other findings include periungual telangiectasias, cuticular hypertrophy, poikiloderma, malar erythema, and photosensitivity.

What systemic manifestations are associated with dermatomyositis?

Systemic manifestations include morning joint stiffness, esophageal dysphagia, lung disease associated with anti-Jo-1, cardiomyopathy, and malignancy, especially ovarian cancer in females.

What labs and tests evaluate dermatomyositis?

Testing includes CPK, aldolase, LDH, transaminases, anti-Jo-1, muscle biopsy, EMG, PFTs, echocardiogram, esophageal studies, and malignancy screening.

What is the most specific muscle enzyme test for dermatomyositis muscle disease?

Creatine phosphokinase, or CPK, is the most specific lab marker for muscle disease in dermatomyositis.

What is scleroderma?

Scleroderma is a multisystem autoimmune disease in which fibroblasts overproduce collagen, causing fibrosis and sclerotic changes of the skin and internal organs such as lungs, heart, and GI tract.

What are the major categories of scleroderma?

Scleroderma is categorized as localized scleroderma, called morphea, and systemic scleroderma, which includes limited disease such as CREST/acrosclerosis and progressive systemic sclerosis.

What is morphea?

Morphea is localized scleroderma presenting as violaceous to ivory hardened skin with possible underlying atrophy or depression; it may be solitary, generalized, linear, en coup de sabre, or pansclerotic.

What is en coup de sabre?

En coup de sabre is a linear form of morphea on the head or forehead, named for its “strike of a saber” appearance.

What is limited systemic scleroderma/acrosclerosis?

Limited systemic scleroderma, or acrosclerosis, is limited to the hands, feet, face, and arms.

What does CREST stand for?

CREST stands for Calcinosis, Raynaud’s phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasias.

Which antibody is associated with CREST syndrome?

Anti-centromere antibody is associated with CREST syndrome.

What is progressive systemic sclerosis?

Progressive systemic sclerosis involves skin and internal organs and may cause Raynaud’s as the first manifestation, pulmonary fibrosis, kidney failure, heart attack or heart failure, and mask-like facies with loss of facial lines.

What tests are used for scleroderma?

Testing includes ANA, anti-Scl-70, anti-centromere for CREST, and evaluation for internal organ involvement.

What is sarcoidosis?

Sarcoidosis is a systemic granulomatous disease of unknown etiology, more common in African Americans, primarily affecting the lungs with bilateral hilar lymphadenopathy.

What are key skin findings in sarcoidosis?

Skin findings include granulomatous lesions, lupus pernio, brown-purple papules, and erythema nodosum as the most common nonspecific skin lesion.

What is the histology of sarcoidosis?

Sarcoidosis is characterized by non-caseating granulomas.

What is diascopy in sarcoidosis?

Diascopy is pressing a glass slide on lesions; positive lesions blanch and reveal an “apple-jelly” color.

What labs may support sarcoidosis?

Hypercalcemia and elevated angiotensin-converting enzyme, or ACE, may support sarcoidosis.

What is the significance of erythema nodosum in sarcoidosis?

Erythema nodosum is the most common nonspecific skin lesion in sarcoidosis and is associated with a good prognosis.

What is Behçet’s disease?

Behçet’s disease is characterized by recurrent oral aphthous ulcers plus at least 2 of the following: genital aphthosis, uveitis, nonerosive arthritis, cutaneous pustular vasculitis, or meningoencephalitis.

What genital finding in Behçet’s disease is often misdiagnosed?

Genital aphthosis in Behçet’s disease is commonly misdiagnosed as herpes simplex virus.

What test helps diagnose Behçet’s disease?

The pathergy test supports diagnosis; it is positive when an inflammatory pustule forms 24–48 hours after skin puncture by a needle.

What is Kawasaki disease also called?

Kawasaki disease is also called mucocutaneous lymph node syndrome.

What mnemonic summarizes Kawasaki disease criteria?

“CRASH and Burn”: conjunctival injection, rash, adenopathy, strawberry tongue/oral fissures/lip crusting, hand and foot edema/erythema/induration/desquamation, and fever greater than 5 days.

What is the major feared complication of Kawasaki disease?

The feared complication is ruptured coronary aneurysm; Kawasaki disease affects children under 10 and has about 2% mortality.

How is Kawasaki disease treated?

Treatment includes salicylates and IVIG.

What is graft-versus-host disease?

GVHD occurs when immunocompetent donor cells react against an immunoincompetent recipient due to histoincompatibility, classically after bone marrow transplant.

When does acute GVHD occur and what organs are affected?

Acute GVHD occurs 14–100 days post-bone marrow transplant and affects skin, liver, and GI tract, classically with a maculopapular rash.

What severe skin presentation can acute GVHD mimic?

Severe acute GVHD can progress from maculopapular rash to bullous lesions with toxic epidermal necrolysis-like changes, mimicking Stevens-Johnson syndrome.

When does chronic GVHD occur and how can it affect skin?

Chronic GVHD occurs more than 100 days post-bone marrow transplant, affects many organs, and may cause skin sclerosis.

What is hereditary hemorrhagic telangiectasia?

Hereditary hemorrhagic telangiectasia, or Osler-Weber-Rendu syndrome, is an autosomal dominant disorder with telangiectasias of the mouth and GI tract.

What is an early sign of hereditary hemorrhagic telangiectasia?

Recurrent spontaneous epistaxis is an early sign of hereditary hemorrhagic telangiectasia.

What are diagnostic criteria for hereditary hemorrhagic telangiectasia?

Criteria include recurrent spontaneous nosebleeds, multiple mucocutaneous telangiectasias, visceral AVMs involving GI, pulmonary, cerebral, or hepatic sites, and a first-degree relative with HHT.

What is Gardner syndrome?

Gardner syndrome is an autosomal dominant syndrome with more than 100 adenomatous colorectal polyps with malignant potential plus cutaneous and skeletal findings.

What cutaneous and dental findings suggest Gardner syndrome?

Findings include multiple epidermal cysts, often on the face or scalp and before puberty, osteomas most commonly of the jaw, and dental abnormalities such as supernumerary or unerupted teeth.

What is Peutz-Jeghers syndrome?

Peutz-Jeghers syndrome is an autosomal dominant disorder with multiple hamartomatous GI polyps, spotty melanin pigmentation mostly on the lips and perioral region, and increased risk of GI and non-GI cancers.

What is Cowden syndrome?

Cowden syndrome, or multiple hamartoma syndrome, is an autosomal dominant disorder with GI polyps, warty papules on the face and forearms, multiple hamartomatous tumors in multiple organ systems, and increased breast cancer risk.

What are acrochordons?

Acrochordons are skin tags, outgrowths of normal skin in friction sites such as the neck, axilla, and groin; they are common in adults and associated with obesity, diabetes, and colonic polyps.

What skin findings are associated with cirrhosis?

Cirrhosis may cause jaundice, itching, palmar erythema, spider telangiectasias, and nail changes such as Terry nails.

What are spider telangiectasias?

Spider telangiectasias are vascular lesions with a central arteriole surrounded by smaller vessels, most often on the face, trunk, and upper limbs.

What are Terry nails?

Terry nails occur when the proximal two-thirds of the nail plate appears white; they are nonspecific but can be seen in liver disease.

What is Sister Mary Joseph’s nodule?

Sister Mary Joseph’s nodule is a malignant metastatic umbilical nodule that may be the first sign of pancreatic cancer and is associated with poor prognosis.

What is relapsing polychondritis?

Relapsing polychondritis is an immune-mediated disease with recurrent inflammation of cartilage, especially ears, nose, eyes, joints, and respiratory tract.

What is the initial presentation of relapsing polychondritis?

The initial presentation is often a tender, erythematous, warm, swollen ear.

What cardiovascular complications can occur in relapsing polychondritis?

Relapsing polychondritis may involve the heart with aortic insufficiency, aortic aneurysm, and aortic or mitral valvular disease in about 10% of patients.

What skin findings are associated with chronic renal failure?

Chronic renal failure may cause pale complexion from anemia, generalized hyperpigmentation, xerosis, pruritus, uremic frost, metastatic calcification in skin, and bullous disease of dialysis.

What is uremic frost?

Uremic frost occurs when urea crystals form on the skin because waste products cannot be excreted due to kidney failure.

What is kwashiorkor?

Kwashiorkor is protein malnutrition with major cutaneous findings including peripheral pitting edema, peeling “enamel paint” dermatoses, and depigmented hair bands called flag signs.

What is the “flag sign” in kwashiorkor?

The flag sign is alternating bands of normally colored and depigmented hair caused by intermittent periods of adequate dietary intake restoring hair color.

What is acrodermatitis enteropathica?

Acrodermatitis enteropathica is zinc deficiency due to autosomal recessive partial defect in intestinal zinc absorption, occurring in infants and treated with zinc sulfate.

What are the clinical findings of acrodermatitis enteropathica?

Findings include alopecia, diarrhea, severe growth retardation, frequent infections, ophthalmic disorders, delayed sexual maturation, neuropsychiatric manifestations, and vesiculobullous erythematous dermatitis in acral, perioral, and perirectal areas.

What is dermatitis herpetiformis?

Dermatitis herpetiformis is a cutaneous manifestation of celiac disease/gluten-sensitive enteropathy with intensely pruritic grouped papules and vesicles on extensor surfaces.

What antibodies are associated with dermatitis herpetiformis/celiac disease?

Associated autoantibodies include anti-gliadin, endomysial, reticulin, and tissue transglutaminase antibodies.

How is dermatitis herpetiformis treated?

Treatment includes dapsone and a gluten-free diet, and it typically responds well.

What is pellagra?

Pellagra is niacin, or vitamin B3, deficiency classically causing the 3 D’s: dermatitis, diarrhea, and dementia.

What is Casal’s necklace?

Casal’s necklace is pellagra-associated dermatitis around the neck in a sun-exposed distribution.