Cutaneous Manifestations of Systemic Disease

Constance L. Hayes

OBJECTIVES

After studying this chapter, the reader will be able to:

Describe at least five systemic disorders demonstrating significant cutaneous signs and symptoms.
Identify the cutaneous signs and symptoms common to leukemia/lymphoma.
Discuss the potential skin alterations in the patient with sarcoidosis, hypothyroidism, hyperthyroidism, Behçet disease, graft versus host disease, and diabetes mellitus.
List at least five cutaneous signs of possible internal malignancy.
Discuss education needs for patients with cutaneous lesions related to systemic disease.
Identify common therapeutic modalities for systemic illnesses with cutaneous manifestations.

KEY POINTS

The skin is fundamentally related and integrated with all body systems and functions.
Cutaneous signs and symptoms may be the first indication of a systemic illness.
Dermatology nursing care for patients with systemic illness presents unique challenges requiring a multidisciplinary approach.
Skin changes may precede, follow, or have a parallel course with suspected internal malignancies.
Patients with suspected systemic illness and concurrent skin signs and symptoms require a comprehensive multisystem assessment and relevant diagnostic workup.
Lymphomas exhibit lymphadenopathy with very firm, rubbery lymph nodes.
Nonblanching petechial rashes of acute leukemia have a slower onset associated with anemia, lymphadenopathy, and hepatosplenomegaly when compared to viral or bacterial causes.
Low iodine levels and exposures to goiter-causing agents such as bromide, fluoride, and chlorine need to be investigated in autoimmune thyroiditis.
Even when thyroid-stimulating hormone, T₄ and T₃, levels are normal, evaluate individuals with elevated lipid levels and hypothyroid symptoms by checking thyroid antibodies and adding low-dose thyroid hormone replacement to abate symptoms.
Thyroid dermopathy or localized myxedema is an uncommon manifestation of an autoimmune thyroid disease (Grave disease) seen mostly in the pretibial region (formerly known as pretibial myxedema) but can be found elsewhere. Thyroid dermopathy is nearly always associated with thyroid ophthalmopathy.
Weight loss to a normal body mass index level (18.5 to 24.9 pounds) improves glucose metabolism and reduces cutaneous lesions and metabolic sequelae associated with diabetes mellitus.
All cutaneous sarcoidosis lesions demonstrate an “apple-jelly” semitranslucent yellow-brown color when blanched under a glass slide.

INTERNAL MALIGNANCY: LEUKEMIA/LYMPHOMA

I. OVERVIEW

A. Definition: Cutaneous lesions may develop with internal hematopoietic and lymphoid malignancies, which are classified by dominant cell type, cell maturity, and duration from onset to death (acute vs. chronic). Leukemia classifications describe the type of white blood cell (WBC) multiplying while lymphomas develop from lymph node, spleen, or other organ lymphocytes. Some classifications include the following:

1. Acute myelomonocytic involves monocytosis in the peripheral blood.

2. Monocytic leukemia affects the reticuloendothelial (macrophage) system with an excess of phagocytic cells, macrophages, and monocytes in connective tissues that overrun the blood and accumulate in the lymph nodes and spleen.

3. Acute lymphocytic leukemias exhibit lymphoblast proliferation and enlarged lymphoid tissues, while aleukemic leukemias have no abnormal cells in the blood.

4. Acute myeloblastic leukemia has a proliferation of immature myeloblasts in tissues, organs, and blood; frequently, it is associated with Sweet’s syndrome (SS).

5. Chronic hairy cell leukemia shows hairy cells in reticuloendothelial organs/blood.

6. Non-Hodgkin lymphoma represents multiple cytologic classifications, other than Hodgkin disease, of either nodular or diffuse tumor pattern.

B. Etiology. Unknown for both leukemias and lymphomas; however, some studies may indicate a possible genetic, environmental, or viral link.

C. Pathophysiology

1. Leukemia is characterized by neoplasia of the WBC in the bone marrow, interfering with normal blood cell maturation and resulting in anemia, decreased platelet production, and granulocytopenia.

2. Non-Hodgkin lymphomas show an abnormal proliferation of various cell types—histiocytic, lymphocytic, or mixed. Malignant cells may spread to lymph nodes, bone marrow, liver, spleen, and gastrointestinal (GI) tract.

3. Tumor cells may directly invade the skin manifesting as papules, macules, flat or infiltrated plaques, nodules, or ulcerative skin lesions.

4. As an indirect result of the malignancy, skin lesions may manifest as pallor (anemia), excoriations (pruritus), petechiae (thrombocytopenia), and opportunistic infections such as severe candidiasis (with neutropenia).

D. Incidence

1. Leukemia accounts for 3.1% of all new US cancers and has an annual prevalence reported at 9 per 100,000.

2. Non-Hodgkin’s Lymphoma (NHL) is a broad spectrum of lymphomas. It is three times more common than Hodgkin lymphoma. The majority of cutaneous lymphomas are of T-cell origin due to their function in the skin and lymphoid tissues.

E. Considerations across the life span

1. Acute leukemia is most common in children, while chronic leukemia is more common in adults in the third to sixth decade of life.

2. Non-Hodgkin lymphoma is most common in the fifth and sixth decades of life and it accounts for 7.0% of all childhood cancers.

II. ASSESSMENT

A. History and physical examination

1. A careful review of systems is essential to determine constitutional symptoms such as headaches, fatigue, fever, malaise, easy bruising, hemorrhages, bone or joint pain, and nutritional deficits (anorexia and weight loss with lymphomas with added nausea, vomiting, and diarrhea in leukemias).

2. Skin examination from leukemias and lymphomas may demonstrate both specific and nonspecific lesions.

3. Common physical examination findings may be hepatomegaly, splenomegaly, painless lymphadenopathy (lymphomas or leukemias), and musculoskeletal- or neurological-related pain and weakness (headaches, visual changes, vertigo, tinnitus in leukemia and pain/paresthesias/paralysis of affected nerve pathways) (Figure 21-1).

4. Clinical hematologic abnormalities include anemias, thrombocytopenia, local/systemic infections (respiratory and skin with leukemias), and opportunistic infections.

B. Specific skin changes

1. Most common are rubbery, erythematous/purplish papules, plaques, or nodules, randomly distributed and/or found in mucous membranes. Less common are fleshcolored lesions (Figures 21-2, 21-3, 21-4, 21-5 and 21-6).

2. Least common are lesions similar in appearance to mycosis fungoides (flat plaques, arciform papules, and ulcerated nodules or tumors, most pruritic in plaque stages) (Figures 21-7, 21-8, 21-9 and 21-10).

3. Early skin changes are most common in acute myelomonocytic and monocytic leukemia and include infiltrated, hyperplastic, friable gingiva, bruising or petechiae, and slow healing of cuts.

4. Aleukemic leukemia cutis presents in the skin as erythematous papules or nodules in the absence of malignant cells in the peripheral blood; Leder stain is the key to diagnosis.

C. Nonspecific skin changes

1. Skin and mucous membrane findings attributable to cytopenia include pallor, purpura, gingival bleeding, oral ulcerations, and recurring skin infections.

2. Skin changes in which the pathogenesis is unknown include acute febrile neutrophilic dermatosis (Sweet’s syndrome), atypical pyoderma gangrenosum, generalized pruritus, vasculitis, acquired ichthyosis, vesicular disease, and xanthomas.

D. Differential diagnosis

1. Differentials include viral, bacterial, and fungal infections seen in tuberculosis, cat-scratch fever, sarcoidosis, dermatomyositis, lymphogranuloma venereum, mononucleosis-type syndromes, human immunodeficiency virus (HIV) infection, Kaposi sarcoma, secondary syphilis, serum sickness, and Kawasaki disease.

2. Pseudolymphomas of the skin may manifest as insect infestations or bites, lymphomatoid papulosis, druginduced pseudolymphoma, actinic reticulosis.

E. Diagnostic tests

1. General diagnostic tests include CBC with differential; HIV; rapid plasma reagin (RPR); hepatitis B surface antigen (HBsAg); antinuclear antigen (ANA); mononucleosis serology; purified protein derivative (PPD) skin test; metabolic panel with lipid profile; x-rays/scans of the chest, abdomen, and bone; and, when indicated, lymph node and/or bone marrow biopsy.

FIGURE 21-1. Massive lymphadenopathy in a patient with chronic lymphocytic leukemia. (From Tkachuk, D. C., & Hirschman, J. V. (2007). Wintrobe’s atlas of clinical hematology (p. 154, Fig. 5.1). Philadelphia, PA: Lippincott Williams & Wilkins.)

FIGURE 21-2. Lymphoma/leukemia—purple/red plaques and papules of leukemia cutis—extensor area of arms. (Image provided by Stedman’s.)

FIGURE 21-3. Leukemia cutis in an infant with congenital leukemia. (From Arceci, R., & Weinstein, H. (2005). Neoplasia in the neonate and young infant. In G. B. Avery, (Ed.). Neonatology: Pathophysiology and management of the newborn. Philadelphia, PA: JB Lippincott, with permission.)

FIGURE 21-4. Gingival infiltration of leukemic cells in a patient with acute myeloid leukemia. (From Greer, J. P., Foerster, J., Rodgers, G. M., Paraskevas, F., Glader, B., Arber, D. A., & Means Jr, R. T. (2009). Wintrobe’s clinical hematology (12th ed., p. 1680, Fig. 72.8). Philadelphia, PA: Lippincott Williams & Wilkins.)

FIGURE 21-5. Ocular involvement in a 60-year-old man with chronic lymphocytic leukemia. (From Shields, J. A., & Shields, C. L. (2015). Eyelid, conjunctival, and orbital tumors: An atlas and textbook. Philadelphia, PA: Wolters Kluwer.)

FIGURE 21-6. Cutaneous B-cell lymphoma. Asymptomatic erythematous lavender plaques and tumors on the face and scalp. (From Elder, D. E. (2012). Atlas and synopsis of lever’s histopathology of the skin. Philadelphia, PA: Wolters Kluwer.)

FIGURE 21-7. Cutaneous T-cell lymphoma. Note “smudgy patches.” (Reproduced with permission from Goodheart, H. G. (2009). Photoguide to common skin disorders: Diagnosis and management (3rd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.)

FIGURE 21-8. Cutaneous lymphoma of hand. (From Dr. Barankin Dermatology Collection.)

FIGURE 21-9. Cutaneous T-cell lymphoma: mycosis fungoides with follicular papules and plaques on face. (From Lugo-Somolinos, A., Lee, I., McKinley-Grant, L., Goldsmith, L. A., Papier, A., Adigun, C. G., …, Fredeking, A. (2011). VisualDx: Essential dermatology in pigmented skin. Philadelphia, PA: Wolters Kluwer.)

FIGURE 21-10. Large non-Hodgkin rectal lymphoma eroding through the perianal skin. (From Corman, M. (2012). Corman’s colon and rectal surgery. Philadelphia, PA: Wolters Kluwer.)

2. Skin biopsy will demonstrate specific type of malignant cell but must be correlated with the history, physical exam, and other diagnostic data.

III. COMMON THERAPEUTIC MODALITIES

A. Systemic therapies include multiple modalities—chemotherapy, radiation, immunotherapy, and bone marrow transplant.

1. Supportive systemic therapies possible are antibiotic prophylaxis, blood/platelet transfusions, and/or use of bone marrow growth factors (erythropoietin, granulocyte-macrophage colony-stimulating factor [GM-CSF]).

B. Local therapies utilized are skin radiation therapy (SRT) to specific lesions or intralesional corticosteroid injections.

1. Supportive management includes topicals for pruritus, oral ulceration or bleeding, and emollients and moisturizers after showering for xerosis.

C. Medical interventions treat primary and secondary disease

1. Clinically assess and monitor supportive blood/platelet replacement transfusions when needed.

2. Monitor skin lesions, blood, urine, and pulmonary systems for potential sources of infection; when indicated, obtain appropriate wound, body fluid, or skin cultures for suspected infections.

D. Medication/drug therapy use and monitoring when indicated

1. Add supportive therapy with antibiotic prophylaxis or treatment of infection.

2. Bone marrow growth factors (erythropoietin or human GM-CSF) to treat anemias and prevent fatigue/malaise.

3. Apply topical anesthetic creams to manage possible oral ulcerations.

4. Administer nonaspirin antipyretic or apply cooling blanket for fever.

E. Diet management

1. Promote adequate fluid intake, multivitamin use, and well-balanced diet and add high-protein foods when skin breakdown is evident.

2. Encourage daily intake of vitamin B complex, to include B6, B12, and folate, supplementation due to high bone marrow turnover with leukemias.

3. Encourage frequent, small feedings of soft nonspicy, nonacidic foods when oral ulcerations are present.

4. Cooled foods may be better tolerated until ulcerations resolve.

F. Surgical intervention

1. Selective splenectomy may be utilized to manage chronic lymphocytic leukemia.

G. Supportive skin care

1. Maintain mobility and body positioning to promote skin integrity and prevent skin breakdown.

2. Use nondeodorant, mild skin cleansing agent.

3. Apply emollients to lips to prevent chapping, dryness, bleeding, or pain.

4. Lubricate skin with cream- or ointment-based skin care product after bathing.

5. If incontinent, keep skin clean and dry and use barrier ointment to prevent chaffing, breakdown, and candida organism overgrowth.

6. Assess and treat opportunistic skin infections like candidiasis or herpes infections.

H. Other nursing interventions

1. Maintain good pulmonary toilet to prevent respiratory illness.

2. Maintain healthy oral cavity; identify oral ulcers or lesions for topical treatments.

3. Prevent constipation or bladder infections with effective bowel/bladder elimination plans.

4. If neutropenic or during acute exacerbation, consider reverse isolation to protect patient from infection.

5. Avoid any unnecessary invasive procedures such as venipunctures, injections, and urethral catheterizations.

I. Complementary alternative medicine

1. Arsenic trioxide (intra-venous) is an FDA-approved treatment for acute promyelocytic leukemia.

2. Follow diets that may decrease inflammation within the body such as antiyeast diets, low glycemic diet, and reduced or gluten-free diets.

3. Supplement diets to enhance immune responses against tumor growths with vitamin E, which enhances T-cell-mediated immune function, and vitamin D to help regulate the immune system response by suppressing T-cell proliferation and modulate macrophage functions.

IV. HOME CARE CONSIDERATIONS

A. Continuity of care concerns

1. The home may need to be adapted for the patient’s health needs.

2. Assistance with activities of daily living may be required during treatment or recuperation periods.

3. Home care nurses are beneficial in monitoring patient status and providing ongoing emotional support and physician liaison services.

CUTANEOUS SIGNS OF SYSTEMIC MALIGNANCY: PARANEOPLASTIC DERMATOSES

I. OVERVIEW

A. Definition. Paraneoplastic dermatoses are a heterogeneous group of cutaneous nonmalignant skin disorders (papulosquamous, erythematous, bullous, and others) that may develop in relation to distant tumors, systemic neoplasms, or their metastases. Early recognition of these dermatoses
can direct diagnostic workups for associated malignant neoplasms or tumors.

B. Etiology

1. A wide range of cutaneous signs have become associated with particular cancers—lung, liver, gastrointestinal, ovarian, breast, pancreas, renal-bladder, leukemias, and lymphoma being the most common.

2. Curth postulates, used for several decades, are criteria to associate a dermatosis and malignancy:

a. The malignancy and skin disorder have a concurrent onset and run a parallel course.

b. Treatment success of the cancer resolves the skin disorder and a remission of the malignancy shows cutaneous disorder return.

c. The characteristic cutaneous eruptions are specific to the tumor cell or site causing them.

d. The malignancy and the skin disorder should be demonstrably associated supported by sound case-control studies.

C. Pathophysiology

1. Pathogenesis is unclear but may be due to tumor or neoplasm secretions affecting cutaneous structures or a “cross-reaction” to skin structures by host defense antibodies directed at the tumor or neoplasm.

D. Incidence

1. Paraneoplastic symptoms/syndromes are found in nearly 20% of cancer patients, often being unrecognized.

2. Nearly three in four cancers in patients with assumed paraneoplastic syndromes can be identified with history, physical, and sex-/age-appropriate cancer screens.

3. Recognition of these relatively unusual paraneoplastic dermatoses can lead to early diagnosis of an associated cancer with potential for better outcomes.

E. For common paraneoplastic dermatoses findings, signs, and associated neoplasias, refer to Table 21-1 and Figures 21-11, 21-12, 21-13, 21-14, 21-15, 21-16, 21-17, 21-18, 21-19, 21-20, 21-21, 21-22, 21-23, 21-24, 21-25 and 21-26.

TABLE 21-1 Skin Lesions Associated with Possible Systemic Neoplasia

Lesion	Description	Associated Malignancy	Comment
Acanthosis nigricans (AN)—type I associated with malignancies (Figure 21-11) Acanthosis palmaris (AP) (tripe palms)	Gray-, brown-, or black velvety-textured hyperpigmented plaques found in a symmetric distribution. Common on the face, neck, nipples, and folds of axillae, groin, knees, elbows, waist, umbilicus, and anus. Thickened, velvety palms with dermatoglyphics pronounced.	Mostly adenocarcinoma (stomach 60%) and common in the lung, breast, and Gastro-intestinal/Genito-urinary (GI/GU) tracts. Lung cancer most common when AP only involved; gastric cancer when AP associated with AN.	Rare type of AN, most common in older adults, with no racial predilection, associated with weight loss and quick onset. Rule out other endocrinopathies, familial tendency, or obesity/insulin resistance. AP: 95% occur with cancers; 77% seen with benign AN types.
Acrokeratosis paraneoplastica (Bazex syndrome)—nongenetic type (Figures 21-12 and 21-13)	Violaceous erythema, scaling, and psoriasiform plaques over acral areas. Starts with fingers, toes, nose, and ear helices and then spreads to nails that exhibit longitudinal and horizontal nail ridging with painful paronychia with absence of infection. May see palmoplantar keratoderma with honeycomb appearance.	Upper airway and upper GI tract are the most common, usually as squamous cell carcinoma. Course of skin changes often parallels course of malignancy.	Rare skin condition, psoriasis-like scaling. More common in males than females. May spread to scalp, extremities, or trunk areas.
Carcinoid syndrome	Flushed, erythematous skin occurring in face, head, neck, chest, and epigastric areas from minutes to hours. Recurrent flushing develops telangiectasia and persistent redness. May see scaling in areas of sun-exposed skin (like pellagra).	Carcinoid tumors excrete excess hormones once metastasized to the liver; as an example, hyperserotonemia (serotonin hormone secretion) is a common one.	Symptoms of this serotonin syndrome are flushing, diarrhea, abdominal pain, muscle spasms, shivering, tremors, agitation, confusion, heart palpitations, and low blood pressure. Serotonin tumor marker in urine for diagnosis: 5-hydroxyindole acetic acid (5-HI).
Dermatomyositis (Figures 21-14, 21-15 and 21-16)	Inflammatory myopathy. Heliotrope—periorbital macular, violaceous erythematous rash and edema. Periungual telangiectasia with nail fold overgrowth. Gottron papules on knuckles and phalangeal joints. Diffuse scalp scaling/pruritus. Photo distributed poikiloderma of shoulders, anterior neck, and chest.	Associated with ovarian, lung, colorectal, pancreatic, and nasopharynx carcinoma and with non-Hodgkin lymphoma in Caucasians.	Course is not parallel with skin changes. Malignancy is commonly associated with rapid-onset diabetes mellitus, grossly elevated ESR or creatinine kinase, and lack of Raynaud phenomenon; seen frequently in fifth and sixth decades of life.
Erythema gyratum repens (Figure 21-17)	Gyrate serpiginous erythematous bands—6- to 8-cm rings of irregular shapes—across skin form scales of a “wood grain pattern.”	Variable sites and types of malignancies—none specific.	Skin course parallel to neoplasm. Requires extensive evaluation to determine site. Occurs in all ages and genders equally.
Exfoliative erythroderma (Figure 21-18)	Extensive erythema, scaling, and edema. Dull scarlet color with small, laminated scales that exfoliate profusely. Vesicles and pustules are usually absent.	Cutaneous T-cell or systemic lymphomas, Hodgkin disease, or leukemias. Rare in B-cell lymphoma. Solid tumor association also reported	Concurrent course of skin and tumor burden
Florid cutaneous papillomatosis (FCP) (Figures 21-19 and 21-20)	Numerous warty small papules and larger nodules on the trunk, upper surface of hands, and extremities can spread to face. Pruritus may occur.	Gastric adenocarcinoma most common; others include GU/GI cancers, lung, and non-Hodgkin lymphoma.	FCP has rapid onset, is always associated with internal malignancy, and presents before or at the time of diagnosis. Often occurs simultaneously with AN or Leser-Trélat syndrome. Biopsy so as to distinguish from virus.
Hypertrichosis lanuginosa (malignant down)	Sudden growth of profuse, soft, nonpigmented, fine, downy, hair in a generalized distribution or localized to the face on an adult without signs of virilization. In time, these hairs may become coarser.	Associated with varied sites and cell types. Most common are lung, colon, or breast cancers.	Malignancy often discovered at time of skin change. Must evaluate for neoplastic growth in patients without cause for sudden hair growth (medication or endocrine abnormality).
Migratory thrombophlebitis (also known as Trousseau syndrome)	Inflamed, reddened, recurrent superficial thrombophlebitis affecting veins or arterioles of the neck, chest, abdomen, and legs/feet.	Pancreas, lung, and prostate adenocarcinomas are common—nearly 50% with this syndrome have an underlying cancer.	Blood clotting imbalance thought to be due to chronic, low-grade, intravascular coagulopathy. Secure an abdominal CT scan.
Necrolytic migratory erythema (NME), also known as glucagon syndrome (GS)	Bullous, ring-shaped red blisters that erode, crust, brown markings. Itchy and painful. Glossitis, angular chelitis, cracked dry lips, and nail ridging are common.	Pancreas, slow-growing cancerous tumor of alpha cells that secrete glucagon hormone	Is rare, afflicts adults over age 50. Secure CT of pancreas. Symptoms clear once cancer cleared. Can metastasize, decreasing treatment benefits
Paget disease (PD) of the breast (Figure 21-21)	Unilateral, sharply marginated, erythematous, eczematous plaque affecting nipple. Increased growth may spread to areola and beyond.	Occurs in conjunction with adenocarcinoma of the breast	Considered a malignant infiltrate rather than a paraneoplastic sign and most likely due to migration of malignant cells
Extramammary Paget disease (EMPD; Figure 21-22)	Erythematous, well-demarcated, plaques involving any region of male or female genitalia. Intense pruritus common; hyper- or hypopigmentation lesions of several centimeters size	Genitourinary cancers. Other associated distant cancers can include breast, colon, liver, kidney, gall bladder, or skin.	Much less common than PD; multifocal lesions possible, afflicts adults in sixth and seventh decade of life. Penal-scrotal EMPD is not common in black populations.
Paraneoplastic pemphigus	Bullous lesions. Painful erosive mucosal lesions may appear lichenoid and lips may crust. Skin lesions appear as erythematous macules, lichenoid, erythema multiforme-like, and flaccid bullae.	Thymomas (benign and malignant), non-Hodgkin lymphoma, chronic lymphocytic leukemia, Castleman tumor, and sarcoma	Review chest x-ray carefully for evidence of a thymoma. Bronchiolitis obliterans is a common complication. Course of skin disorder does not parallel the malignancy.
Pityriasis rotunda (PR) type 1	Round or oval, sharply defined, pigmented patches with dry ichthyosis-like scaling that mainly occurs on the trunk, arms, and legs. Fewer than 30 hyperpigmented lesions in PR type 1	Most often occurs with liver and stomach cancer; others include chronic myeloid leukemia, squamous cell carcinoma, and multiple myeloma	Type 1 associated with malignancy in Black, Asian, or Italian patients older than 60 years. Comprehensive workup needed to assess malignancy
Porphyria cutanea tarda (PCT; Figures 21-23 and 21-24)	Hyperpigmentation of sun-exposed areas, hypertrichosis and, less commonly, intact noninflammatory vesicles/bullae that rupture easily	Hepatic tumors	Requires careful liver, iron, and ferritin evaluations. Onset most common in midlife. Associated with viral and alcoholic hepatitis
Sudden-onset multiple seborrheic keratosis (Figure 21-25)	Raised papules or plaques with “stuckon” appearance. Lesion surface is usually wart-like.	Intra-abdominal adenocarcinoma	May occur simultaneously with AN. Known as sign of Leser-Trélat syndrome
Sweet’s syndrome – an acute febrile neutrophilic dermatosis; (Figure 21-26)	Sharply marginated, tender, raised, erythematous plaques, 2-10 cm diameter. Typically involve face, neck, trunk, and extremities with burning but not pruritic sensation	Myelogenous leukemia or plasma cell dyscrasia; underlying solid tumors are rare—but are mainly GU, breast (in women), and gastrointestinal (in men).	Associated with fever and anemia, course parallels that of the leukemia. Solitary or ulcerative lesions are frequently associated with malignancies.
CT, computed tomography; GI, gastrointestinal; GU, genitourinary
Data from Bolongnia, Shaffer, Duncan, Ko (2014); James, Berger, Elson (2011); Lebwohl, Heymann, Berth-Jones, Coulson (2014).

FIGURE 21-11. Acanthosis nigricans. (From Goodheart, H. P. (2003). Goodheart’s photoguide of common skin disorders (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.)

FIGURE 21-12. Bazex syndrome with psoriasiform dermatitis. (From NYU Langone Medical Center, Ronald O. Perelman Department of Dermatology slide collection.)

FIGURE 21-13. Bazex syndrome; foot involvement. (From NYU Langone Medical Center, Ronald O. Perelman Department of Dermatology slide collection.)

FIGURE 21-14. Dermatomyositis: Gottron sign. (From Dr. Barankin Dermatology Collection.)

FIGURE 21-15. Dermatomyositis: nail fold with dilated capillary loops. (Image provided by Stedman’s.)

FIGURE 21-16. Juvenile dermatomyositis: hand. (From Dr. Barankin Dermatology Collection.)

FIGURE 21-17. Erythema gyratum repens. (From NYU Langone Medical Center, Ronald O. Perelman Department of Dermatology slide collection.)

FIGURE 21-18. Exfoliative erythroderma with widespread erythema and scaling. (From Goodheart, H. P. (2003). Goodheart’s photoguide of common skin disorders (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.)

FIGURE 21-19. Oral florid papillomatosis (squamous cell carcinoma). (From Goodheart, H. P. (2010). Goodheart’s same-site differential diagnosis: A rapid method of diagnosing and treating common skin disorders. Philadelphia, PA: Wolters Kluwer.)

FIGURE 21-20. Cutaneous papillomatosis: confluent and reticulated on the trunk with hyperpigmented papules surrounding islands of normal skin. (From Craft, N., Taylor, E., Tumeh, P. C., Fox, L. P., Goldsmith, L. A., Papier, A., …, Rosenblum, M. (2010). VisualDx: Essential adult dermatology. Philadelphia, PA: Wolters Kluwer.)

FIGURE 21-21. Paget nipple. Ulceration of nipple with progression onto areola. (From Harris, J. R., Lippman, M. E., & Osborne, C. K. (2014). Diseases of the breast (5th ed.). Philadelphia, PA: Wolters Kluwer.)

FIGURE 21-22. Extramammary Paget disease has caused an irregular but well-marginated erythematous erosive patch with slightly indurated edges in this patient. (Courtesy of Arnold Medved, MD.)

FIGURE 21-23. Porphyria cutanea tarda (note blisters on hands and frontal forehead; also characteristic excess hair on lateral cheeks). (From Goodheart, H. P. (2010). Goodheart’s same-site differential diagnosis: A rapid method of diagnosing and treating common skin disorders. Philadelphia, PA: Wolters Kluwer.)

FIGURE 21-24. Skin eruptions in a patient with porphyria cutanea tarda. (From Ferrier, D. R. (2013). Lippincott illustrated reviews: Biochemistry. Philadelphia, PA: Wolters Kluwer.)

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