Cutaneous Presentation of Systemic Diseases

SBE (sub-acute bacterial endocarditis)

Emboli trapped at the capillary beds show as micro- hemorrhages or infarcts.

Nail bed pathology

Differentiate from Hutchinson’s Sign for melanoma

Superficial Spreading: most common and seen on back and trunk. Can become nodular

Nodular: vertical growth phase

Acrolentigenous: seen on digits and subungual areas, more common blacks

Lentigo Maligna: least common, usually on face or other actinic exposure areas

Clubbing of nails can be seen in pachydermoperiostosis syndrome (seen in lung cancer— bronchogenic or alveolar cell carcinoma

Bazex’s syndrome (yellow nails with violaceous color of skin) seen in lung cancer

Terry’s Nails (ground glass appearance to nails) can be seen in CHF

Acute Leukemias (non-lymphoblastic)

Uncontrolled proliferation of hematopoietic cells with malignant cells filling marrow and other tissue and with the reduced production of erythrocytes, granulocytes and megakaryocytes, anemia, infection and hemorrhage results.80% incidence of ALL (acute lymphoblastic leukemia) in children80% incidence of ANLL (acute non-lymphocytic leukemia) in adultsClassification is via predominant neoplastic cell line (lymphoblastic or non-lymphoblastic [myeloblastic/monocytic])Sub-classified by the FAB (French/American/British) group

Acute Leukemias (non-lymphoblastic)Etiologies include chromosomal damage from radiation, chemicals (e.g., benzene and alkylating agents used in therapy), congenital diseases (e.g., Down’s syndrome), and chronic bone marrow diseases (e.g., myeloid metaplasia), congenital predisposition, and congenital immunodeficiency syndromes (e.g., ataxia-telangiectasia).

In acute leukemia, the uncontrolled proliferation of hematopoietic cells in the bone marrow and peripheral blood eventually replace the marrow and invade other tissues and organs. The manifestation of the disease results in diminished production of erythrocytes, granulocytes and megakaryocytes with resulting anemia, infection and hemorrhage.

As the degree of marrow and other organ involvement progresses, symptoms of fatigue, ecchymosis, buccal lesions and infection increase. Peri-rectal infections are often seen in ANLL with skin and gum infiltrates seen an acute monocytic leukemia. Rheumatic symptoms occur commonly with ALL, as well as lymphadenopathy and hepatosplenomegaly. Patients with ANLL can have unusual masses in the soft tissue and nodal sites, as a precursor of overt marrow and peripheral blood invasion and may be mistaken for lymphoma. These are called myeloblastomas.

Acute Leukemias (non-lymphoblastic)

Degree of organ or marrow involvement will dictate the types of lesionsSkin and gum infiltrates are commonly seen in AML (Candida albicans)Leukemic infiltration of the gums in AMOLPeri-rectal infections are frequent in ANLLJoint swelling and bone pain with rheumatic symptoms is seen in ALL

Acute Leukemias (non-lymphoblastic)

AMOL lesion (1)ANLL leukemia cutis (2)Leukemic infiltrates at the eye (3)Acute leukemia at the anterior shin (4)AML with petechial hemorrhages (5)

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Acute Leukemias (non-lymphoblastic)

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• Sweet’s syndrome: acute febrile neutrophilic dermatosis. Seen in AML or AMOL (acute monocytic leukemia). Seen here in ANLL (acute non-lymphocytic leukemia [1])

• Usually drug-induced or following a viral illness in the young

• 10% incidence of underlying cancer, most commonly myelocytic leukemia (1-3)

• Nonmyelocytic leukemia and lymphoma have been reported (4)

• Other cutaneous presentations:– Arm in AML (2)– Leg in AML (3)– Scalp in ANLL (4)

Acute Leukemias (non-lymphoblastic)

• Bone involvement: acute leukemic infiltration with necrosis marked by yellow opacification of the marrow with surrounding hyperemic tissue.

Acute Leukemias (non-lymphoblastic)

• AML-induced Pseudomonas pyocyanea infection at the foot and hand

• Streptococcal cellulitis at the neck and face all induced by the neutropenia from the prior chemotherapy for AML

Acute Leukemia (lymphoblastic)

• B-cell lymphoma (Burkitt’s)

• T-cell (Sézary syndrome)

Graft vs. Host Disease• Acute leukemia therapy (allogenic

bone marrow transplant) can result in morbidity/mortality. This is seen as a range from papulosquamous eruptions or desquamation of the skin, with the palmar and plantar areas most commonly involved, as in this patient with AML

Chronic Leukemias• CLL (chronic lymphocytic leukemia)

presenting as lymphadenopathy (1)• CLL converting to DLCL (diffuse large cell

lymphoma) with trunk lesion which shows B-immunoblastic type diffuse large cell lymphoma or Richter’s syndrome (2)

• CLL-induced herpes zoster lesions (3) with buccal infection with Candida albicans (4)

• CLL-induced pharyngeal tonsil enlargement (5)

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Chronic Leukemias• CML can present with

hyperviscosity syndrome and hepato- splenomegaly. Note the splenic infarct (white spot at the surface of the spleen

Lichen Planus• Inflammatory, muccocutaneous condition with common

morphology• Long-term oral mucosal lesions (1) have an increased

risk of developing squamous cell carcinoma. Same with genital lesions.

• Causes include drug eruptions and HCV infection, although most cases are idiopathic

• Treatment includes oral and topical steroids, Soriatane, PUVA and possibly Dapsone and Plaquenil

• Usual presentation is a violaceous polygonal flat-top papule (2) and plaque with white scales (Wickham’s striae)

• Variations include:– a hypertrophic version (3)– Vesiculobullous (4) and actinic type (5)

variants– Nail and subungual presentation

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Internal Malignancies• The most common benign

cutaneous lesions most likely to be associated with internal malignancy include:

1. Dermatomyositis2. Acanthosis nigricans3. Necrotic migratory erythema4. Herpes zoster

Other diseases:–Multiple eruptive seborrheic keratoses–Sweet’s syndrome–Erythroderma–Xanthoma–Pemphigus vulgaris–Erythema gyratum repens

Dermatomyositis• Associated with internal neoplasia with a

27% incidence rate.• Prevalence in women• Ovarian, breast, lung, stomach and colon

cancers are most often seen in association with dermatomyositis with the cutaneous presentation identical regardless of cancer type

• Polymyositis appears clinically as dermatomyositis, but has none of the increased cancer risks.

•Diagnosis is a combination of muscle abnormalities and characteristic heliotrope rash (periorbital reddish-purple flush which predates the muscle weakness by weeks, months or even years•A violaceous erythema appearing over the knuckles, elbows and knees (Gottron’s sign) with raised, flat-topped papules on the knuckles (Gottron’s papules)

Heliotrope Rash

Acanthosis Nigicans

• Associated with GI cancer (adenocarcinoma is the most common)

• Also associated with Diabetes Mellitus and obesity

Necrotic Migratory Erythema

• Associated with α-cell islet tumors, with 60% malignant (glucagonoma)

• Seen with Diabetes Mellitus

• Glossitis also often seen

Herpes Zoster

• With disseminated, severe and ulcerative disease, may signal cancer in 75% to 80% of people

• Usual association is with lymphoma and leukemia

Xanthoma Planum

• Has a high association with Multiple Myeloma

• No lipid dyscrasias in these patients

Multiple Eruptive Seborrheic Keratoses

• Benign neoplasms usually• Abrupt onset associated with

underlying cancer is called the sign of Leser-Trélat

•Most commonly associated with adenocarcinoma of the stomach•Others include leukemia, mycosis fungoides, hepatoma and carcinoma of lung and breast

Erythroderma

• Usually seen in psoriasis, atopic dermatitis, drug- induced allergic reactions

• 15% of cases are with underlying malignant disorders such as Sézary syndrome or mycosis fungoides

Pemphigus Vulgaris• Autoimmune disease with

bullous lesions which rupture leaving a denuded patch called “Nikolsky’s sign”

• Can be associated with thymoma and myasthenia gravis

• Paraneoplastic pemphigus is associated with cancer, most commonly non-Hodgkin’s lymphoma with 90% mortality due to sepsis or respiratory failure

Erythema Gyratum Repens

• Wood grain pattern in the skin

• 90% associated with internal cancer

• Most commonly lung• Less commonly esophagus

and breast

Breast Cancer

• Cutaneous presentation seen in 1% of patient population.

• Can be direct extension of the tumor or of local or distant metastasis

• Direct extension most common with breast cancer and oral cancer

Ovarian Cancer

• Malignant, cutaneous lesions indicative of systemic cancer are typically nodular with a firm consistency and are red, plum- colored or hyperpigmented

• Ulceration of the lesions suggest an underlying cancer

Other Signs• Flushing, usually evident in the face and upper chest, most commonly

accompanies carcinoid tumors of the intestine• Palmar erythema, usually associated with advanced liver failure, may

also accompany primary or metastatic malignant liver disease• Direct extension of breast cancer to the skin may be accompanied by

telangiectasia• Purpuric lesions may be a manifestation of disseminated intravascular

coagulation induced by cancer. DIC can also cause acral gangrene in foot and hand.

• Thrombophlebitis is usually migratory when associated with cancer

Gonococcal Septicemia

• Seen with Disseminated Gonnococcal infection DGI

• Present with pyrexia, polyarthralgias and skin lesions which may be papular, petechial, pustular, hemorrhagic or necrotic and usually found on the distal extremities

Syphilis• Primary syphilis usually presents as a chancre

with bilateral inguinal adenopathy which may persist for months

• Secondary syphilis presents with skin lesions (1) which move from macules to papules and pustular erosions with the palms and soles often affected (2)

• Intertrigenous areas can manifest with papules enlarging to moist lesions called condyloma lata (3), which are highly infectious

• Tertiary syphilis is neurosyphilis and presents largely as changes in mentation, with sensorium and autonomic deficit (demyelination of posterior columns), Charcot joint and Argyll Robertson pupils (accommodation but not light response)

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Lupus• Tissues and cells are damaged by

deposition of pathogenic antibodies and immune complexesβ-cell hyperactivity, production of autoantibodies with specificity for nuclear antigenic determinants and abnormalities in T-cell function occur

Meningococcal septicemia• 30%-50% of those who develop

meningococcal disease have bacteremia without meningitis

• Prodromal syndrome of tussis, cephalgia, with sudden spike of pyrexia with 75% developing petechia with distal necrosis sometimes developing

• Waterhouse-Friderichsen syndrome in fulminant disease (10-20%)

Disseminated Fat Necrosis• When associated with pancreatic

cancer can cause lesions (1) from release of pancreatic enzymes into the blood or lymph, causing distal necrosis

• An acute panniculitis (2), causing tender nodules in subcutaneous fat and may be suppurative (nodular fat necrosis)

• As panniculitis may result from a variety of conditions, Weber- Christian disease is not a specific entity

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Polyarteritis

• Inflammation of and damage to blood vessels, compromise of vessel lumen and resulting ischemia

• May be primary or manifestation of disease or secondary to another disease process

Tuberculosis

• Lupus vulgaris is a granulomatous disease of the skin usually in long- standing, untreated disease elsewhere

• Erythema nodosum may be present, although more common in other diseases

Diabetes

• Diabetic bullosis• Necrobiosis

lipoidica diabeticorum

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